Analysed genes:

• ACE (rs4646994)
• ACTN3 (rs1815739)

Literature:

• Alvarez R, Terrados N, Ortolano R, Iglesias-Cubero G, Reguero JR, Batalla A, Cortina A, Fernandez-Garcia B, Rodriguez C, Braga S, Alvarez V & Coto E (2000). Genetic variation in the renin-angiotensin system and athletic performance. Eur J Appl Physiol 82, 117–120.
• Blanchard A, Ohanian V, Critchley D (1989) The structure and function of α-actinin. J Muscle Res Cell Motil 10:280–289
• Broos S et al. History-dependent force, angular velocity and muscular endurance in ACTN3 genotypes. Eur J Appl Physiol. 2015 Mar 12.
• Collins M, Xenophontos SL, Cariolou MA, Mokone GG, Hudson DE, Anastasiades L & Noakes TD (2004). The ACE gene and endurance performance during the South African Ironman Triathlons. Med Sci Sports Exerc 36, 1314–1320.
• Eur J Hum Genet. 2008 Mar:16(3):391-4. Epub 2007 Nov 28. The ACTN3 R577X nonsense allele is under-represented in elite-level strength athletes. Roth SM1, Walsh S, Liu D, Metter EJ, Ferrucci L, Hurley BF.
• Eynon N et al. Genes for elite power and sprint performance: ACTN3 leads the way. Sports Med. 2013 Sep,43(9):803-17. doi: 10.1007/s40279-013-0059-4.
• Gayagay G, Yu B, Hambly B, Boston T, Hahn A, Celermajer DS & Trent RJ (1998). Elite endurance athletes and the ACE I allele – the role of genes in athletic performance. Hum Genet 103, 48–50.
• Kikuchi et al. The ACTN3 R577X polymorphism is associated with muscle power in male Japanese athletes. J Strength Cond Res. 2014 Jul,28(7):1783-9.
• Kikuchi N et al. The ACTN3 R577X genotype is associated with muscle function in a Japanese population. Appl Physiol Nutr Metab. 2015
  Apr,40(4):316-22.
• MacArthur et al. A gene for speed? The evolution and function of alpha-actinin-3. Bioessays. 2004 Jul,26(7):786-95
• MacArthur DG, North KN: ACTN3: a genetic influence on muscle function and athletic performance. Exerc Sport Sci Rev 2007: 35: 30
• Moran CN, Yang N, Bailey ME et al: Association analysis of the ACTN3 R577X polymorphism and complex quantitative body composition and
  performance phenotypes in adolescent Greeks. Eur J Hum Genet 2007:15: 88
• Nazarov IB, Woods DR, Montgomery HE, Shneider OV, Kazakov VI, Tomilin NV & Rogozkin VA (2001). The angiotensin converting enzyme I/D polymorphism in Russian athletes. Eur J Hum Genet 9, 797–801.
• Niemi et al. Mitochondrial DNA and ACTN3 genotypes in Finnish elite endurance and sprint athletes. Eur J Hum Genet. 2005 Aug,13(8):965-9.
• Niemi AK, Majamaa K: Mitochondrial DNA and ACTN3 genotypes in Finnish elite endurance and sprint athletes. Eur J Hum Genet 2005: 13: 965
• Norman et al. ACTN3 genotype and modulation of skeletal muscle response to exercise in human subjects. J Appl Physiol (1985). 2014 May
  1,116(9):1197-203
• North KN, Yang N, Wattanasirichaigoon D, Mills M, Easteal S, Beggs AH (1999) A common nonsense mutation results in α-actinin-3 deficiency in the general population. Nat Genet 21:353–354
• Santiago C et al. ACTN3 genotype in professional soccer players. Br J Sports Med. 2008 Jan,42(1):71-3. Epub 2007 Jun 5
• Scanavini D, Bernardi F, Castoldi E, Conconi F & Mazzoni G (2002). Increased frequency of the homozygous II ACE genotype in Italian Olympic endurance athletes. Eur J Hum Genet 10, 576–577.
• Vincent B, De Bock K, Ramaekers M et al: The ACTN3 (R577X) genotype is associated with fiber type distribution. Physiol Genomics
• Yang et al. ACTN3 genotype is associated with human elite athletic performance. Am J Hum Genet. 2003 Sep,73(3):627-31. Epub 2003 Jul 23.
• Yang N, MacArthur DG, Gulbin JP et al: ACTN3 genotype is associated with human elite athletic performance. Am J Hum Genet 2003: 73: 627
• Zanoteli et al. Deficiency of muscle alpha-actinin-3 is compatible with high muscle performance. J Mol Neurosci. 2003 Feb,20(1):39-42.

Analysed genes:

• NRF-2 (rs7181866)
• VEGF (rs2010963)
• ADRB2 (rs1042714)
• ADRB2 (rs1042713)
• CRP (rs3093066) 

Literature:

• Akhmetov II et al. Polymorphism of the vascular endothelial growth factor gene (VEGF) and aerobic performance in athletes. Fiziol Cheloveka. 2008 Jul-Aug,34(4):97-101.
• Akhmetov II et al. The combined impact of metabolic gene polymorphisms on elite endurance athlete status and related phenotypes. Hum Genet. 2009 Dec,126(6):751-61.
• Bouchard C et al. Genomic scan for maximal oxygen uptake and its response to training in the HERITAGE Family Study. J Appl Physiol (1985). 2000 Feb,88(2):551-9.
• Eynon N et al. NRF2 intron 3 A/G polymorphism is associated with endurance athletes’ status. J Appl Physiol (1985). 2009 Jul,107(1):76-9.
• Garatachea N et al. Genes, physical fitness and ageing. Ageing Res Rev. 2013 Jan,12(1):90-102.
• He Z et al. NRF2 genotype improves endurance capacity in response to training. Int J Sports Med. 2007 Sep,28(9):717-21. Epub 2007 Mar 15.
• Kullo IJ et al. Markers of inflammation are inversely associated with VO2 max in asymptomatic men. J Appl Physiol (1985). 2007 Apr,102(4):1374-9.
• Kuo et al. Association of cardiorespiratory fitness and levels of C-reactive protein: Data from the National Health and Nutrition Examination Survey 1999–2002. Int J Cardiol. 2007 Jan 2,114(1):28-33.
• McCole SD et al. Beta2- and beta3-adrenergic receptor polymorphisms and exercise hemodynamics in postmenopausal women. J Appl Physiol (1985). 2004 Feb,96(2):526-30.
• Moore GE et al. Obesity gene variant and elite endurance performance. Metabolism. 2001 Dec,50(12):1391-2.
• Prior SJ et al. DNA sequence variation in the promoter region of the VEGF gene impacts VEGF gene expression and maximal oxygen consumption. Am J Physiol Heart Circ Physiol. 2006 May,290(5):H1848-55. Epub 2005 Dec 9.
• Wagoner LE et al. Polymorphisms of the beta(2)-adrenergic receptor determine exercise capacity in patients with heart failure. Circ Res. 2000 Apr 28,86(8):834-40.
• Wolfarth B et al. Association between a beta2-adrenergic receptor polymorphism and elite endurance performance. Metabolism. 2007 Dec,56(12):1649-51.

Analysed genes:

• GSTM1 (Null Allele)
• GSTP1 (rs1695)
• GSTT1 (Null Allele)
• SOD2 ( (rs4880)
• GPX1 (rs1050450)
• NQO1 (rs1800566)

Literature:

• Bhatti et al. Lead exposure, polymorphisms in genes related to oxidative stress and risk of adult brain tumors. Cancer Epidemiol Biomarkers Prev. Jun 2009, 18(6): 1841–1848.
• Chen et al. GPx-1 polymorphism (rs1050450) contributes to tumor susceptibility: evidence from meta-analysis. J Cancer Res Clin Oncol. 2011 Oct,137(10):1553-61.
• Fischer et al. Association between genetic variants in the Coenzyme Q10 metabolism and Coenzyme Q10 status in humans. Published online Jul 21, 2011.
• Freriksen et al. Genetic polymorphism 609C>T in NAD(P)H:quinone oxidoreductase 1 enhances the risk of proximal colon cancer. J Hum Genet. 2014 May 15.
• Funke et al. Genetic Polymorphisms in Genes Related to Oxidative Stress (GSTP1, GSTM1, GSTT1, CAT, MnSOD, MPO, eNOS) and Survival of Rectal Cancer Patients after Radiotherapy. J Cancer Epidemiol. 2009, 2009: 302047.
• Hong et al. GPX1 gene Pro200Leu polymorphism, erythrocyte GPX activity, and cancer risk. Mol Biol Rep. 2013 Feb,40(2):1801-12.
• Jablonska E et al. Association between GPx1 Pro198Leu polymorphism, GPx1 activity and plasma selenium concentration in humans. Eur J Nutr. 2009 Sep,48(6):383-6.
• Karunasinghe et al. Serum selenium and single-nucleotide polymorphisms in genes for selenoproteins: relationship to markers of oxidative stress in men from Auckland, New Zealand. Genes Nutr. 2012 Apr,7(2):179-90.
• McWilliams et al. Glutathione S-transferase M1 (GSTM1) deficiency and lung cancer risk. Cancer Epidemiol Biomarkers Prev 1995,4:589-594.
• Miller et al. An association between glutathione S-transferase P1 gene polymorphism and younger age at onset of lung carcinoma. Cancer. 2006 Oct 1,107(7):1570-7.
• Soerensen et al. The Mn-superoxide dismutase single nucleotide polymorphism rs4880 and the glutathione peroxidase 1 single nucleotide polymorphism rs1050450 are associated with aging and longevity in the oldest old. Mech Ageing Dev. 2009 May,130(5):308-14.
• Sreeja et al. Glutathione S-transferase M1, T1 and P1 polymorphisms: susceptibility and outcome in lung cancer patients. J Exp Ther Oncol. 2008,7(1):73-85.
• Steinbrecher et al. Effects of selenium status and polymorphisms in selenoprotein genes on prostate cancer risk in a prospective study of European men. Cancer Epidemiol Biomarkers Prev. 2010 Nov,19(11):2958-68.
• Stücker et al. Genetic polymorphisms of glutathione S-transferases as modulators of lung cancer susceptibility. Carcinogenesis. 2002 Sep, 23(9):1475-81.
• Sutton et al. The manganese superoxide dismutase Ala16Val dimorphism modulates both mitochondrial import and mRNA stability. Pharmacogenet Genomics. 2005 May,15(5):311-9.
• Tang et al. Association between the rs1050450 glutathione peroxidase-1 (C > T) gene variant and peripheral neuropathy in two independent samples of subjects with diabetes mellitus. Nutr Metab Cardiovasc Dis. 2012 May,22(5):417-25.
• Xiong et al. Association study between polymorphisms in selenoprotein genes and susceptibility to Kashin-Beck disease. Osteoarthritis Cartilage. 2010 Jun,18(6):817-24.

Analysed genes:

• IL6 (rs1800795)
• TNF-α (rs1800629) 
• IL1RN (rs419598)
• CRP (rs3093066)
• IL6R (rs2228145)
• GDF5 (rs143383)
• Col1A1 (rs1800012)
• Col5A1 (rs12722)

Literature:

• Collins M et al. Genetic risk factors for musculoskeletal soft tissue injuries. Med Sport Sci. 2009,54:136-49.
• Collins M et al. The COL5A1 genotype is associated with range of motion measurements. Scand J Med Sci Sports. 2009 Dec,19(6):803-10.
• Collins M et al. The COL1A1 gene and acute soft tissue ruptures. Br J Sports Med. 2010 Nov,44(14):1063-4
• Galicia JC et al. Polymorphisms in the IL-6 receptor (IL-6R) gene: strong evidence that serum levels of soluble IL-6R are genetically influenced. Genes Immun. 2004 Sep,5(6):513-6.
• Ge W et al. The GDF5 SNP is associated with meniscus injury and function recovery in male Chinese soldiers. Int J Sports Med. 2014 Jun,35(7):625-8.
• Gray SR et al. The response of circulating levels of the interleukin-6/interleukin-6 receptor complex to exercise in young men. Cytokine. 2009 Aug,47(2):98-102.
• Helge JW et al. The effect of graded exercise on IL-6 release and glucose uptake in human skeletal muscle. J Physiol. 2003 Jan 1, 546(Pt 1):299-305.
• Huuskonen A et al. A common variation in the promoter region of interleukin-6 gene shows association with exercise performance. J Sports Sci Med. 2009 Jun 1,8(2):271-7.
• Iglesias-Linares A et al. Postorthodontic external root resorption is associated with IL1 receptor antagonist gene variations. Oral Dis. 2012 Mar,18(2):198-205.
• Jones SA et al. IL-6 transsignaling: the in vivo consequences. J Interferon Cytokine Res. 2005 May,25(5):241-53.
• Kiah McCabe et al. Can Genetics Predict Sports Injury? The Association of the Genes GDF5, AMPD1, COL5A1 and IGF2 on Soccer Player Injury Occurrence, Sports (Basel). 2018 Mar, 6(1): 21
• Khoschnau S et al. Type I collagen alpha1 Sp1 poly-morphism and the risk of cruciate ligament ruptures or shoulder dislocations. Am J Sports Med 2008, 36:2432–2436.
• Lakka HM et al. The TNF-alpha G-308A polymorphism is associated with C-reactive protein levels: the HERITAGE Family Study. Vascul Pharmacol. 2006 May,44(5):377-83.
• Maffulli N et al. The genetics of sports injuries and athletic performance. Muscles Ligaments Tendons J. 2013 Aug 11,3(3):173-89.
• Mokone GG et al. The COL5A1 gene and Achilles tendon pathology. Scand J Med Sci Sports. 2006 Feb,16(1):19-26.
• Moldoveanu AI et al. Exercise elevates plasma levels but not gene expression of IL-1beta, IL-6, and TNF-alpha in blood mononuclear cells. J Appl Physiol (1985). 2000 Oct,89(4):1499-504.
• Neubauer O et al. Recovery after an Ironman triathlon: sustained inflammatory responses and muscular stress. Eur J Appl Physiol. 2008 Oct,104(3):417-26.
• Obisesan TO et al. C-Reactive Protein Genotypes Affect Baseline, but not Exercise Training–Induced Changes, in C-Reactive Protein Levels. Arterioscler Thromb Vasc Biol. 2004 Oct, 24(10): 1874–1879.
• Pedersen BK et al. The metabolic role of IL-6 produced during exercise: is IL-6 an exercise factor? Proc Nutr Soc. 2004 May,63(2):263-7.
• Phillips T et al. A dietary supplement attenuates IL-6 and CRP after eccentric exercise in untrained males. Med Sci Sports Exerc. 2003 Dec,35(12):2032-7.
• Posthumus M et al. Genetic risk factors for anterior cru-ciate ligament ruptures: COL1A1 gene variant. Br J Sports Med 2009,43:352–356
• Posthumus M et al. Components of the transforming growth factor-beta family and the pathogenesis of human Achilles tendon pathology–a genetic association study. Rheumatology (Oxford). 2010 Nov,49(11):2090-7.
• Reich Db (2007). Health, Aging and Body Composition (Health ABC) Study: Admixture mapping of an allele affecting interleukin 6 soluble receptor and interleukin 6 levels. Am J Hum Genet. 80(4): 716-726.
• Robson-Ansley P et al. (2011). The effect of carbohydrate ingestion on plasma interleukin-6, hepcidin and iron concentrations following prolonged exercise. Cytokine. 53(2):196-200.
• September AV et al. Variants within the COL5A1 gene are associated with Achilles tendinopathy in two populations. Br J Sports Med. 2009 May,43(5):357-65.
• Valdes AM et al. Association of the DVWA and GDF5 polymorphisms with osteoarthritis in UK populations. Ann Rheum Dis. 2009 Dec,68(12):1916-20.
• Wójtowicz A et al. IL1B and DEFB1 Polymorphisms Increase Susceptibility to Invasive Mold Infection After Solid-Organ Transplantation. J Infect Dis. 2015 May 15,211(10):1646-57.
• X. Wu et al. IL-1 receptor antagonist gene as a predictive biomarker of progression of knee osteoarthritis in a population cohort. Osteoarthritis Cartilage. 2013 Jul, 21(7): 930–938.
• Yamin C et al. IL6 (-174) and TNFA (-308) promoter polymorphisms are associated with systemic creatine kinase response to eccentric exercise. Eur J Appl Physiol. 2008 Oct,104(3):579-86.

Analysed genes:

• MMP1 (rs1799750)

Literature – Genetics:

• Benbow U et al. High levels of MMP-1 expression in the absence of the 2G single nucleotide polymorphism is mediated by p38 and ERK1/2 mitogenactivated protein kinases in VMM5 melanoma cells. J Cell Biochem. 2002,86(2):307-19.
• Fujimoto T et al. A single nucleotide polymorphism in the matrix metalloproteinase-1 (MMP-1) promoter influences amnion cell MMP-1 expression and risk for preterm premature rupture of the fetal membranes.
• Rutter JL et al. A single nucleotide polymorphism in the matrix metalloproteinase-1 promoter creates an Ets binding site and augments transcription. Cancer Res. 1998 Dec 1,58(23):5321-5.
• Tower GB et al. Erk 1/2 differentially regulates the expression from the 1G/2G single nucleotide polymorphism in the MMP-1 promoter in melanoma cells. Biochim Biophys Acta. 2002 Apr 24,1586(3):265-74.
• Tower GB et al. The 2G single nucleotide polymorphism (SNP) in the MMP-1 promoter contributes to high levels of MMP-1 transcription in MCF-7/ADR breast cancer cells. Breast Cancer Res Treat. 2003 Nov,82(2):75-82.
• Tower GB et al. Fra-1 targets the AP-1 site/2G single nucleotide polymorphism (ETS site) in the MMP-1 promoter. Eur J Biochem. 2003 Oct,270(20):4216-25.
• Vincenti MP et al. Transcriptional regulation of collagenase (MMP-1, MMP-13) genes in arthritis: integration of complex signaling pathways for the recruitment of gene-specific transcription factors. Arthritis Res. 2002,4(3):157-64. Epub 2001 Nov 23.

Literature – Action Plan:

• Alleva, Tomasetti, Sartini, Emanuelli, Nasole, Di Donato, Borghi, Santarelly, Neuzil, “α-Lipoic Acid
  Modulates Extracellular Matrix and Angiogenesis Gene Expression in Non-Healing Wounds Treated with Hyperbaric Oxygen Therapy”, Molecular medicine, 14, pp: 175-183, 2007
• Astner, Wu, Chen et al., “Dietary lutein/zeaxanthin partially reduces photoaging and photocarcinogenesis in chronically UVBirradiated Skh-1 hairless mice,” Skin Pharmacology and Physiology, vol. 20, no. 6, pp. 283–291, 2007.
• Arch Dermatol Res. 2007 Oct:299(8):373-9. Epub 2007 Aug 21. Regulation of the extracellular matrix remodeling by lutein in dermal fibroblasts, melanoma cells, and ultraviolet radiation exposed fibroblasts. Philips N1, Keller T, Hendrix C, Hamilton S, Arena R, Tuason M, Gonzalez S.
• Benbow U, Tower GB, Wyatt CA, Buttice G, Brinckerhoff CE. High levels of MMP-1 expression in the absence of the 2G single nucleotide polymorphism is mediated by p38 and ERK1/2 mitogen-activated protein kinases in VMM5 melanoma cells. J Cell Biochem. 2002:86:307–19
• Breast Cancer Res Treat. 2003 Nov:82(2):75-82. The 2G single nucleotide polymorphism (SNP) in the MMP-1 promoter contributes to high levels of MMP-1 transcription in MCF-7/ADR breast cancer cells. Tower GB1, Coon CI, Brinckerhoff CE.
• Cancer Res. 2001 Feb 15:61(4):1296-8. Invasiveness of cutaneous malignant melanoma is influenced by matrix metalloproteinase 1 gene polymorphism. Ye S1, Dhillon S, Turner SJ, Bateman AC, Theaker JM, Pickering RM, Day I, Howell WM.
• Enzyme Research Volume 2011 (2011), Article ID 427285, 4 pages, Beneficial Regulation of Matrix Metalloproteinases for Skin Health Neena Philips,1 Susan Auler,1 Raul Hugo,1 and Salvador Gonzalez
• Free Radic Biol Med. 1999 Oct:27(7-8):729-37. Age-dependent increase of collagenase expression can be reduced by alphatocopherol via protein kinase C inhibition. Ricciarelli R1, Maroni P, Ozer N, Zingg JM, Azzi A.
• Fujimoto T, Parry S, Urbanek M, Sammel M, Macones G, Kuivaniemi H, Romero R, Strauss JF., 3rd A single nucleotide polymorphism in the matrix metalloproteinase-1 (MMP-1) promoter influences amnion cell MMP-1 expression and risk for preterm premature rupture of the fetal membranes. J Biol Chem. 2002:277:6296–6302
• Kim, Kim, Park, Kim, Kwon, Park, Lee, Kim, Lee, “α-Lipoic acid inhibits matrix metalloproteinase-9 expression by inhibiting NF-κB transcriptional activity”, Experimental and Molecular Medicine , 39, pp: 106-113, 2007
• Kim, Oh, Kim, and Hwang, “Fucosterol inhibits matrix metalloproteinase expression and promotes
  type-1 procollagen production in UVB-induced HaCaT cells,” Photochem. Photobiol., 89, pp:911–918, 2013
• Lee, Lee, Lee, Son, Chung, Baek, and Kim, “A glycosidic spinasterol from Koreana stewartia
  promotes procollagen production and inhibits matrix metalloproteinase-1 expression in UVB-irradiated human dermal fibroblasts,”Biol. Pharm. Bull., 34, pp: 768–773, 2011
• Makpol, Jam, Khor, Ismail, Yusof, and Ngah, “Comparative Effects of Biodynes, TocotrienolRich Fraction, and Tocopherol in Enhancing Collagen Synthesis and Inhibiting Collagen Degradation in Stress-Induced Premature Senescence Model of Human Diploid Fibroblasts,” Oxidative Medicine and Cellular Longevity, pp. 1-8, 2013.
• Matsui Y, Maeda M, Nakagami W, Iwata H. The involvement of matrix metalloproteinases and inflammation in lumbar disc herniation. Spine. 1998:23:863–8.
• Molecular Cell Biology. 4th edition. Section 22.3 Collagen: The Fibrous Proteins of the Matrix, Lodish H, Berk A, Zipursky SL, et al. New York: W. H. Freeman: 2000.
• Murphy G, Nagase H. Progress in matrix metalloproteinase research. Mol Aspects Med. 2008:29:290–308.
• Nusgens BV. Topically applied vitamin C enhances the mRNA level of collagens I and III, their processing enzymes and tissue inhibitor of matrix metalloproteinase 1 in the human dermis. J Invest Dermatol. 2001 Jun;116(6):853-9.
• Nutrition for Healthy Skin: Strategies for Clinical and Cosmetic Practice, Philippe Humbert, Springer Science & Business Media, 08.11.2010
• Palombo P, Fabrizi G, Ruocco V, Ruocco E, Flühr J, Roberts R, and Morganti P. Beneficial long-term effects of combined oral/topical antioxidant treatment with carotenoids lutein and zeaxanthin on human skin: A double-blinded, placebocontrolled study in humans. J Skin Pharmacol and Physiol 20: 199-210. 2007.
• Pathol Biol (Paris). 2003 Dec:51(10):569-73. Down-regulation of tissue inhibitor of matrix metalloprotease-1 (TIMP-1) in aged human skin contributes to matrix degradation and impaired cell growth and survival. Hornebeck W1.
• Philips, Cancer cell growth and extracellular matrix remodeling mechanism of ascorbate; beneficial modulation by P. leucotomos. Anticancer Res. 2009 Aug;29(8):3233-8.
• Philips, Conte, Chen et al., “Beneficial regulation of matrixmetalloproteinases and their inhibitors, fibrillar collagens and transforming growth factor-β by Polypodium leucotomos, directly or in dermal fibroblasts, ultraviolet radiated fibroblasts, and melanoma cells,” Archives of Dermatological Research, vol. 301, no. 7, pp. 487–495, 2009
• Philips, Keller, Hendrix et al., “Regulation of the extracellular matrix remodeling by lutein in dermal fibroblasts, melanoma cells, and ultraviolet radiation exposed fibroblasts,” Archives of Dermatological Research, vol. 299, no. 8, pp. 373–379, 2007.
• Rutter JL, Mitchell TI, Buttice G, Meyers J, Gusella JF, Ozelius LJ, Brinckerhoff CE. A single nucleotide polymorphism in the matrix metalloproteinase-1 promoter creates an Ets binding site and augments transcription. Cancer Res. 1998:58:5321–5325.
• Textbook of Functional Medicine. 2005; ;Gig Harbor, Wash.
• Toshio Fujimoto, Samuel Parry, Margrit Urbanek, Mary Sammel, George Macones, Helena Kuivaniemi‖, Roberto Romero‖ and Jerome F. Strauss, A Single Nucleotide Polymorphism in the Matrix Metalloproteinase-1 (MMP-1) Promoter Influences Amnion Cell MMP-1 Expression and Risk for Preterm Premature Rupture of the Fetal Membranes, February 22, 2002, The Journal of Biological Chemistry, 277, 6296-6302.
• Tower GB, Coon CC, Benbow U, Vincenti MP, Brinckerhoff CE. Erk 1/2 differentially regulates the expression from the 1G/2G single nucleotide polymorphism in the MMP-1 promoter in melanoma cells. Biochim Biophys Acta. 2002:1586:265–74.
• Tower GB, Coon CI, Belguise K, Chalbos D, Brinckerhoff CE. Fra-1 targets the AP-1 site/2G single nucleotide polymorphism (ETS site) in the MMP-1 promoter. Eur J Biochem. 2003:270:4216–25
• Vincenti MP, Brinckerhoff CE. Transcriptional regulation of collagenase (MMP-1, MMP-13) genes in arthritis: integration of complex signaling pathways for the recruitment of gene-specific transcription factors. Arthritis Res. 2002:4:157–64
• Wingerath T, Sies H, and Stahl W. Xanthophyll esters in human skin. Arch Biochem Biophys 355: 271-274., 1998
• Yıldırım Baş F. Effect of alpha lipoic acid on smoking-induced skin damage. Cutan Ocul Toxicol. 2016 Apr 8:1-7.

Analysed genes:

• CYP1A2 (rs762551)

Literature – Genetics:

• Palacios N et al. Polymorphisms of caffeine metabolism and estrogen receptor genes and risk of Parkinson’s disease in men and women. Parkinsonism Relat Disord. 2010 Jul,16(6):370-5.
• Palatini P et al. CYP1A2 genotype modifies the association between coffee intake and the risk of hypertension. J Hypertens. 2009 Aug,27(8):1594-601.
• Sache C et al. Functional significance of a C-->A polymorphism in intron 1 of the cytochrome P450 CYP1A2 gene tested with caffeine. Br J Clin Pharmacol. 1999 Apr,47(4):445-9.
• Thorn CF et al. PharmGKB summary: caffeine pathway. Pharmacogenet Genomics. 2012 May,22(5):389-95.

Literature – Action Plan:

• Amino Acids. 2008 Nov:35(4):731-8. Prolidase-dependent regulation of collagen biosynthesis. Surazynski A1, Miltyk W, Palka J, Phang JM.
• Am J Pathol. 2007 Nov:171(5):1451-61. Chronic ultraviolet B irradiation causes loss of hyaluronic acid from mouse dermis because of downregulation of hyaluronic acid synthases. Dai G1, Freudenberger T, Zipper P, Melchior A, Grether-Beck S, Rabausch B, de Groot J, Twarock S, Hanenberg H, Homey B, Krutmann J, Reifenberger J,Fischer JW.
• Asian Pac J Cancer Prev. 2015:16(8):3559-63. Breast Cancer Association with CYP1A2 Activity and Gene Polymorphisms – a Preliminary Casecontrol Study in Tunisia. Imene A1, Maurice AJ, Arij M, Sofia P, Saad S.
• Belin, Kaya, Burtey, and Fontes, “Ascorbic Acid and gene expression: another example of regulation of gene expression by small molecules?,” Curr. Genomics, vol. 11, no. 1, pp. 52–57, Mar. 2010.
• Biochem Biophys Res Commun. 2013 Jan 11:430(2):579-84. Ascorbic acid enhances the expression of type 1 and type 4 collagen and SVCT2 in cultured human skin fibroblasts. Kishimoto Y1, Saito N, Kurita K, Shimokado K, Maruyama N, Ishigami A.
• Boyera, Galey, and Bernard, “Effect of vitamin C and its derivatives on collagen synthesis and cross-linking by normal human fibroblasts,” Int. J. Cosmet. Sci., vol. 20, no. 3, pp. 151–158, Jun. 1998.
• Clin Interv Aging. 2014 Oct 13:9:1747-58. Daily consumption of the collagen supplement Pure Gold Collagen® reduces visible signs of aging. Borumand M1, Sibilla S1.
• Drug Des Devel Ther. 2014 Oct 15:8:1923-8. Influence of caffeine and hyaluronic acid on collagen biosynthesis in human skin fibroblasts. Donejko M1, Przylipiak A1, Rysiak E2, Głuszuk K2, Surażyński A2
• Exp Dermatol. 2003 Jun:12(3):237-44. Topical ascorbic acid on photoaged skin. Clinical, topographical and ultrastructural evaluation: double-blind study vs. placebo. Humbert PG1, Haftek M, Creidi P, Lapière C, Nusgens B, Richard A, Schmitt D, Rougier A, Zahouani H.
• Fitzpatrick and Rostan, “Double-blind, half-face study comparing topical vitamin C and vehicle for
  rejuvenation of photodamage,” Dermatol. Surg. Off. Publ. Am. Soc. Dermatol. Surg. Al, vol. 28, no. 3, pp. 231–236, Mar. 2002.
• Geesin, Darr, Kaufman, Murad, and Pinnell, “Ascorbic acid specifically increases type I and type III
  procollagen messenger RNA levels in human skin fibroblast,” J. Invest. Dermatol., vol. 90, no. 4, pp. 420–424, Apr. 1988.
• Guang Pu Xue Yu Guang Pu Fen Xi. 2012 Dec:32(12):3299-303. The study of absorption efficiency and restoring effects of collagen and ascorbic acid on aged skin by fluorescence and reflection spectroscopy. Yang BW1, Lin YM, Wang SY, Yeh DC.
• Heber, Markovic, and Hayes, “An immunohistological study of anhydrous topical ascorbic acid compositions on ex vivo human skin,” J. Cosmet. Dermatol., vol. 5, no. 2, pp. 150–156, Jun. 2006.
• Humbert, Haftek, Creidi, Lapière, Nusgens, Richard, Schmitt, Rougier, and Zahouani, “Topical
  ascorbic acid on photoaged skin. Clinical, topographical and ultrastructural evaluation: double-blind study vs. placebo,” Exp. Dermatol., vol. 12, no. 3, pp. 237–244, Jun. 2003.
• J Cosmet Dermatol. 2011 Mar:10(1):15-23. Folic acid and creatine improve the firmness of human skin in vivo. Fischer F1, Achterberg V, März A, Puschmann S, Rahn CD, Lutz V, Krüger A, Schwengler H, Jaspers S, Koop U, Blatt T, Wenck H, Gallinat S.
• J Cosmet Dermatol. 2012 Dec:11(4):310-7. Stability, transdermal penetration, and cutaneous effects of ascorbic acid and its derivatives. Stamford NP1.
• J Cosmet Dermatol. 2014 Dec:13(4):307-14. doi: 10.1111/jocd.12116. A new dermal filler made of cross-linked and auto-crosslinked hyaluronic acid in the correction of facial aging defects. Sparavigna A1, Fino P, Tenconi B, Giordan N, Amorosi V, Scuderi N.
• J Cosmet Laser Ther. 2014 Jun:16(3):132-7. Effects of collagen tripeptide supplement on skin properties: a prospective, randomized, controlled study. Choi SY1, Ko EJ, Lee YH, Kim BG, Shin HJ, Seo DB, Lee SJ, Kim BJ, Kim MN.
• J Dermatol Sci. 2014 Sep:75(3):173-82. Sodium L-ascorbate enhances elastic fibers deposition by fibroblasts from normal and pathologic human skin. Hinek A1, Kim HJ2, Wang Y2, Wang A2, Mitts TF3.
• J Int Soc Sports Nutr. 2012: 9: 7. The influence of a CYP1A2 polymorphism on the ergogenic effects of caffeine, Christopher J Womack,corresponding author1 Michael J Saunders,1 Marta K Bechtel,2 David J Bolton,1 Michael Martin,1 Nicholas D Luden,1 Wade Dunham,2 and Melyssa Hancock 2
• J Invest Dermatol. 2001 Jun:116(6):853-9.Topically applied vitamin C enhances the mRNA level of collagens I and III, their processing enzymes and tissue inhibitor of matrix metalloproteinase 1 in the human dermis.Nusgens BV1, Humbert P, Rougier A, Colige AC, Haftek M, Lambert CA, Richard A, Creidi P, Lapière CM.
• J Med Food. 2014 Jul:17(7):810-6. Supplementating with dietary astaxanthin combined with collagen hydrolysate improves facial elasticity and decreases matrix metalloproteinase-1 and -12 expression: a comparative study with placebo. Yoon HS1, Cho HH, Cho S, Lee SR, Shin MH, Chung JH.
• Kaplan, Moloney, Troy, Dickens, and Pinnell, “A new stabilized ascorbic acid solution:
  Percutaneous absorption and effect on relative collagen synthesis,” J Cutan. Ag Cosm Derm, vol. 1, pp. 88–92, 1988.
• Mol Cell Biochem. 2015 May:403(1-2):51-60. The mechanism of oxythiamine-induced collagen biosynthesis in cultured fibroblasts. Szoka L1, Karna E, Palka J.
• Mol Ther. 2013 Jul:21(7):1335-44. Topical application of recombinant type VII collagen incorporates into the dermalepidermal junction and promotes wound closure. Wang X1, Ghasri P, Amir M, Hwang B, Hou Y, Khalili M, Lin A, Keene D, Uitto J, Woodley DT, Chen M.
• Nat Prod Res. 2015 May 18:1-7. Prolidase-dependent mechanism of (Z)-8,9-epoxyheptadeca-1,11,14-triene-induced inhibition of collagen biosynthesis in cultured human skin fibroblasts. Szoka L1, Karna E, Nazaruk J, Palka JA.
• Necas, Bartosikova, Brauner, Kolar, “Hyaluronic Acid (Hyaluronan): A review”, Veterinarni Medicina, 53, 397-411, 2008
• Nusgens, Humbert, Rougier, Colige, Haftek, Lambert, Richard, Creidi, and Lapière,
  “Topically applied vitamin C enhances the mRNA level of collagens I and III, their processing enzymes and tissue inhibitor of matrix metalloproteinase 1 in the human dermis,” J. Invest. Dermatol., vol. 116, no. 6, pp. 853–859, Jun. 2001.
• Nusgens, Humbert, Rougier, Richard, and Lapière, “Stimulation of collagen biosynthesis by topically applied vitamin C,” Eur. J. Dermatol. EJD, vol. 12, no. 4, pp. XXXII–XXXIV, Aug. 2002.
• Park, Ock, Kim, Park, Lee, Choi, Cho, Lee, Cho, and Cho, “Vitamin C
  attenuates ERK signalling to inhibit the regulation of collagen production by LL-37 in human dermal fibroblasts,” Exp. Dermatol., vol. 19, no. 8, pp. e258–e264, Aug. 2010.
• Phillips, Combs, and Pinnell, “Effects of ascorbic acid on proliferation and collagen synthesis in relation to the donor age of human dermal fibroblasts,” J. Invest. Dermatol., vol. 103, no. 2, pp. 228–232, Aug. 1994.
• Phillips, Tajima, and Pinnell, “Ascorbic acid and transforming growth factor-beta 1 increase collagen biosynthesis via different mechanisms: coordinate regulation of pro alpha 1(I) and Pro alpha 1(III) collagens,” Arch. Biochem. Biophys., vol. 295, no. 2, pp. 397–403, Jun. 1992.
• Photochem Photobiol. 2011 Sep-Oct:87(5):1105-12. doi: 10.1111/j.1751-1097.2011.00959.x. Epub 2011 Jul 28. Ultraviolet-B irradiation induces differential regulations of hyaluronidase expression and activity in normal human keratinocytes. Kurdykowski S1, Mine S, Bardey V, Danoux L, Jeanmaire C, Pauly G, Brabencova E, Wegrowski Y, Maquart FX.
• Skin Pharmacol Physiol. 2014:27(1):47-55. Oral supplementation of specific collagen peptides has beneficial effects on human skin physiology: a double-blind, placebo-controlled study. Proksch E1, Segger D, Degwert J, Schunck M, Zague V, Oesser S.
• Talanta. 2015 Aug 1:140:36-41. Quantification of caffeine in human saliva by Nuclear Magnetic Resonance as an alternative method for cytochrome CYP1A2 phenotyping. Schievano E1, Finotello C2, Navarini L3, Mammi S2.
• Tajima and Pinnell, “Ascorbic acid preferentially enhances type I and III collagen gene transcription in human skin fibroblasts,” J. Dermatol. Sci., vol. 11, no. 3, pp. 250–253, Mar. 1996.

Analysed genes:

• MC1R (rs885479)
• MC1R (rs11547464)
• MC1R (rs1805006)
• MC1R (rs1805007)
• STXBP5L (rs322458)

Literature- Genetics:

• Bastiaens MT et al. Melanocortin-1 receptor gene variants determine the risk of nonmelanoma skin cancer independently of fair skin and red hair. Am J Hum Genet 2001,68(4):884–94.
• Box NF et al. Melanocortin-1 receptor genotype is a risk factor for basal and squamous cell carcinoma. J Invest Dermatol 2001,116(2):224–9.
• Cordoba-Lanus E et al. MC1R gene variants and sporadic malignant melanoma susceptibility in the Canary Islands population. Arch Dermatol Res. 2014 Jan,306(1):51-8.
• Elfakir A et al. Functional MC1R-Gene Variants Are Associated with Increased Risk for Severe Photoaging of Facial Skin. Journal of Investigative Dermatology (2010) 130, 1107–1115.
• Journal of Investigative Dermatology (2013) 133, 929–935, A Genome-Wide Association Study in Caucasian Women Points Out a Putative Role of the STXBP5L Gene in Facial Photoaging, Sigrid Le Clerc1,11, Lieng Taing1,11, Khaled Ezzedine2,3, Julie Latreille4,12, Olivier Delaneau1,5, Toufik Labib1, Cédric Coulonges1, Anne Bernard4,12, Safa Melak1, Wassila Carpentier6, Denis Malvy2,7, Randa Jdid4,12, Pilar Galan2, Serge Hercberg2,8, Frederique
  Morizot4,12, Christiane Guinot4,9,12, Erwin Tschachler4,10,11,12 and Jean F Zagury1,11
• Kennedy C et al. Melanocortin 1 receptor (MC1R) gene variants are associated with an increased risk for cutaneous melanoma which is largely independent of skin type and hair color. . J Invest Dermatol 2001,117(2):294–300.
• Matichard E et al. Melanocortin 1 receptor (MC1R) gene variants may increase the risk of melanoma in France independently of clinical risk factors and UV exposure. J Med Genet 2004,41(2):e13.
• Nan H et al. Genome-wide association study identifies novel alleles associated with risk of cutaneous basal cell carcinoma and squamous cell carcinoma. Hum Mol Genet. 2011 Sep 15,20(18):3718-24.
• Palmer JS et al. Melanocortin-1 receptor polymorphisms and risk of melanoma: is the association explained solely by pigmentation phenotype? Am J Hum Genet 2000,66(1):176–86.
• Puig-Butille JA et al. Distribution of MC1R variants among melanoma subtypes: p.R163Q is associated with lentigo maligna melanoma in a Mediterranean population. Br J Dermatol. 2013 Oct,169(4):804-11
• Raimondi S et al. MC1R variants, melanoma and red hair color phenotype: a meta-analysis. Int J Cancer. 2008 Jun 15,122(12):2753-60.
• Rouzaud F et al. MC1R and the response of melanocytes to ultraviolet radiation. Mutat Res. 2005 Apr 1,571(1-2):133-52.
• Scherer D et al. MC1R variants associated susceptibility to basal cell carcinoma of skin: interaction with host factors and XRCC3 polymorphism. Int J Cancer. 2008 Apr 15,122(8):1787-93.
• Swope VB et al. Significance of the Melanocortin 1 and Endothelin B Receptors in Melanocyte Homeostasis and Prevention of Sun-Induced Genotoxicity. Front Genet. 2016 Aug 17,7:146.
• Valverde P et al. The Asp84Glu variant of the melanocortin 1 receptor (MC1R) is associated with melanoma. Human Molecular Genetics, 1996, Vol. 5, No. 10 1663–1666.
• van der Velden PA et al. Melanocortin-1 receptor variant R151C modifies melanoma risk in Dutch families with melanoma. Am J Hum Genet
  2001,69(4):774–9.
• Wendt J et al. Human Determinants and the Role of Melanocortin-1 Receptor Variants in Melanoma Risk Independent of UV Radiation Exposure. JAMA Dermatol. 2016 Jul 1,152(7):776 82.
• Wong TH et al. The relation between melanocortin 1 receptor (MC1R) variation and the generation of phenotypic diversity in the cutaneous response to ultraviolet radiation. Peptides. 2005 Oct,26(10):1965-71.

Literature – Action Plan:

• Br J Dermatol. 2011 Nov: 165(5): 1011–1021.The determinants of periorbital skin ageing in participants of a melanoma case–control study in the U.K. M Suppa,*† F Elliott,* JS Mikeljevic,‡ Y Mukasa,‡ M Chan,* S Leake,* B Karpavicius,* S Haynes,* E Bakker,§ K Peris,† JH Barrett,* DT Bishop,* and JA Newton Bishop*
• Br J Dermatol. Author manuscript, Distribution of MC1R variants among melanoma subtypes: p.R163Q is associated with Lentigo Maligna Melanoma in a Mediterranean population, J.A. Puig-Butillé,1,2 C. Carrera,1,3 R. Kumar,4 Z. Garcia-Casado,5 C. Badenas,1,2 P. Aguilera,1,3 J. Malvehy,1,3 E. Nagore,6 and S. Puig1,3
• Eberlein-König and Ring, “Relevance of vitamins C and E in cutaneous photoprotection,” Journal of Cosmetic Dermatology, vol. 4, pp. 4-9, 2005.
• Hongmei Nan, et al. Genome-wide association study identifies novel alleles associated with risk of cutaneous basal cell carcinoma and squamous cell carcinoma. Human Molecular Genetics, 2011, Vol. 20, No 18
• J Invest Dermatol. 2010 Apr:130(4):1107-15. Functional MC1R-gene variants are associated with increased risk for severe photoaging of facial skin. Elfakir A1, Ezzedine K, Latreille J, Ambroisine L, Jdid R, Galan P, Hercberg S, Gruber F, Malvy D, Tschachler E, Guinot C.
• Journal of Investigative Dermatology (2010) 130, 1107–1115: Functional MC1R-Gene Variants Are Associated with Increased Risk for Severe Photoaging of Facial Skin: Anissa Elfakir1, Khaled Ezzedine2,3, Julie Latreille1, Laurence Ambroisine1, Randa Jdid4, Pilar Galan2, Serge Hercberg2, Florian Gruber5, Denis Malvy2,6, Erwin Tschachler5,7 and Christiane Guinot1,8
• Journal of Investigative Dermatology (2013) 133, 929–935, A Genome-Wide Association Study in Caucasian Women Points Out a Putative Role of the STXBP5L Gene in Facial Photoaging, Sigrid Le Clerc, Lieng Taing, Khaled Ezzedine, Julie Latreille, Olivier Delaneau, Toufik Labib, Cédric Coulonges, Anne Bernard, Safa Melak, Wassila Carpentier, Denis Malvy, Randa Jdid, Pilar Galan, Serge Hercberg, Frederique Morizot, Christiane Guinot, Erwin Tschachler and Jean F Zagury
• Makpol, Jam, Khor, Ismail, Yusof, and Ngah, “Comparative Effects of Biodynes, TocotrienolRich Fraction, and Tocopherol in Enhancing Collagen Synthesis and Inhibiting Collagen Degradation in Stress-Induced Premature Senescence Model of Human Diploid Fibroblasts,” Oxidative Medicine and Cellular Longevity, pp. 1-8, 2013.
• Musalmah, Nizrana, Fairuz, NoorAini, Azian, Gapor, and Wan Ngah, “Comparative Effects
  of Palm Vitamin E and a-Tocopherol on Healing and Wound Tissue Antioxidant Enzyme Levels in Diabetic Rats,” Lipids, Vol. 40, no. 6, pp. 575-580, 2005.
• Mutat Res. 2005 Apr 1:571(1-2):133-52. MC1R and the response of melanocytes to ultraviolet radiation. Rouzaud F1, Kadekaro AL, Abdel-Malek ZA, Hearing VJ.
• Paloma Valverde et al. The Asp84Glu Variant of the Melanocortin 1 Receptor (MC1R) is Associated with Melanoma. Human Molecular Genetics, 1996, Vol. 5, No. 10 1663–1666
• Panin, Strumia, and Ursini, “Topical α-Tocopherol Acetate in the Bulk Phase: Eight Years of Experience in Skin Treatment,” Ann. N.Y. Acad. Sci. vol. 1031, pp. 443–447, 2004.
• Pedrelli, Lauriola, and Pigatto, “Clinical evaluation of photoprotective effect by a topical antioxidants combination [tocopherols and tocotrienols],” Journal of the European Academy of Dermatology and Venereology, vol. 26, pp. 1449-1453, 2012.
• Photochem Photobiol Sci. 2013 Jan:12(1):197-202. The evolution of sunscreen products in the United States–a 12-year cross sectional study. Wang SQ1, Tanner PR, Lim HW, Nash JF.
• Pigment Cell Melanoma Res. 2012 May: 25(3): 384–394. Inherited variants in the MC1R gene and survival from cutaneous melanoma: a BioGenoMEL study, John R Davies, Juliette Randerson-Moor, Kairen Kukalizch, Mark Harland, Rajiv Kumar, Srinivasan Madhusudan, Eduardo Nagore, Johan Hansson, Veronica Höiom, Paola Ghiorzo, Nelleke A Gruis, Peter A Kanetsky, Judith Wendt, Dace Pjanova, Susana Puig, Philippe Saiag, Dirk Schadendorf, Nadem Soufir, Ichiro Okamoto, Paul Affleck, Zaida García-Casado, Zighereda Ogbah,11,12 Aija Ozola,10 Paola Queirolo,19 Antje
  Sucker,14 Jennifer H Barrett,1 Remco van Doorn,7 D Timothy Bishop,1 and Julia Newton-Bishop1
• Podda, Weber,’ Maret G. Traber, and Lester Packer, “Simultaneous determination of tissue tocopherols, tocotrienols, ubiquinols, and ubiquinones,” Journal of Lipid Research, vol. 37, pp. 893-901, 1996.
• Shapiro and Saliou, “Role of vitamins in skin care,” Nutrition, vol. 17, issue 10, pp. 839–844,October 2001.
• Skin Pharmacol Physiol. 2005 Nov-Dec:18(6):253-62. Epub 2005 Aug 19. Sunscreens – which and what for? Maier T1, Korting HC.
• Tavakkol, Nabi, Soliman, and Polefka, “Delivery of vitamin E to the skin by a novel liquid skin cleanser: Comparison of topical versus oral supplementation,” J. Cosmet. Sci., vol. 55, pp.177-187, March 2004.
• Thiele, Hsieh, and Ekanayake-Mudiyanselage, “Vitamin E: Critical Review of Its Current Use in Cosmetic and Clinical Dermatology,” Dermatol Surg,vol. 31, pp. 805-813, 2005.
• Weber, Podda, Rallis, Thiele, Traber, and Packer, “Efficacy of Topically Applied Tocopherols and
  Tocotrienols in Protection of Murine Skin from Oxidative Damage Induced by UV-Irradiation” Free Radical Biology & Medicine, Vol. 22, No. 5, pp. 761–769, 1997.

Analysed genes:

• MC1R (rs885479)
• MC1R (rs11547464)
• MC1R (rs1805006)
• MC1R (rs1805007)
• STXBP5L (rs322458)

Literature – Genetics:

• Bastiaens M et al. The melanocortin-1-receptor gene is the major freckle gene. Hum Mol Genet 2001,10(16):1701–8.
• Box NF et al. Melanocortin-1 receptor genotype is a risk factor for basal and squamous cell carcinoma. J Invest Dermatol 2001,116(2):224–9.
• Duffy DL et al. Interactive effects of MC1R and OCA2 on melanoma risk phenotypes. Hum Mol Genet 2004,13(4):447–61.
• Elfakir A et al. Functional MC1R-Gene Variants Are Associated with Increased Risk for Severe Photoaging of Facial Skin. Journal of Investigative Dermatology (2010) 130, 1107–1115.
• Kennedy C et al. Melanocortin 1 receptor (MC1R) gene variants are associated with an increased risk for cutaneous melanoma which is largely independent of skin type and hair color. J Invest Dermatol 2001,117(2):294–300.
• Le Clerc S et al. A genome-wide association study in Caucasian women points out a putative role of the STXBP5L gene in facial photoaging. J Invest Dermatol. 2013 Apr,133(4):929-35.
• Palmer JS et al. Melanocortin-1 receptor polymorphisms and risk of melanoma: is the association explained solely by pigmentation phenotype? Am J Hum Genet 2000,66(1):176–86.
• Puig-Butille JA et al. Distribution of MC1R variants among melanoma subtypes: p.R163Q is associated with Lentigo Maligna Melanoma in a Mediterranean population. Br J Dermatol. 2013 Oct, 169(4)
• Rouzaud F et al. MC1R and the response of melanocytes to ultraviolet radiation. Mutat Res. 2005 Apr 1,571(1-2):133-52.
• Smith R et al. Melanocortin 1 receptor variants in an Irish population. J Invest Dermatol 1998,111(1):119–22
• Sturm RA et al. Genetic association and cellular function of MC1R variant alleles in human pigmentation. Ann N Y Acad Sci 003,994:348–58.
• Suppa M et al. The determinants of periorbital skin ageing in participants of a melanoma case-control study in the U.K. Br J Dermatol. 2011 Nov,165(5):1011-21.
• Wong TH et al. The relation between melanocortin 1 receptor (MC1R) variation and the generation of phenotypic diversity in the cutaneous response to ultraviolet radiation. Peptides. 2005 Oct,26(10):1965-71.
• Yamaguchi K et al. Association of melanocortin 1 receptor gene (MC1R) polymorphisms with skin reflectance and freckles in Japanese. J Hum Genet. 2012 Nov 26,57(11):700-8.

Literature – Action Plan:

• Am J Pathol. 2007 Nov:171(5):1451-61. Chronic ultraviolet B irradiation causes loss of hyaluronic acid from mouse dermis because of downregulation of hyaluronic acid synthases. Dai G1, Freudenberger T, Zipper P, Melchior A, Grether-Beck S, Rabausch B, de Groot J, Twarock S, Hanenberg H, Homey B, Krutmann J, Reifenberger J,Fischer JW.
• Arch Plast Surg. 2015 May:42(3):282-7. doi: 10.5999/aps.2015.42.3.282. Epub 2015 May 14. Rejuvenating Effects of Facial Hydrofilling using Restylane Vital. Lee BM1, Han DG1, Choi WS2.
• Bauman, “Cosmetic Dermatology – Principles and Pactice”, second edition, ISBN: 978-0-07-164128-9
• Br J Dermatol. Author manuscript, Distribution of MC1R variants among melanoma subtypes: p.R163Q is associated with Lentigo Maligna Melanoma in a Mediterranean population, J.A. Puig-Butillé,1,2 C. Carrera,1,3 R. Kumar,4 Z. Garcia-Casado,5 C. Badenas,1,2 P. Aguilera,1,3 J. Malvehy,1,3 E. Nagore,6 and S. Puig1
• Br J Dermatol. 2011 Nov: 165(5): 1011–1021.The determinants of periorbital skin ageing in participants of a melanoma case–control study in the U.K. M Suppa,*† F Elliott,* JS Mikeljevic,‡ Y Mukasa,‡ M Chan,* S Leake,* B Karpavicius,* S Haynes,* E Bakker,§ K Peris,† JH Barrett,* DT Bishop,* and JA Newton Bishop*
• J Clin Aesthet Dermatol. 2014 Mar:7(3):27-9. Efficacy of a New Topical Nano-hyaluronic Acid in Humans. Jegasothy SM1, Zabolotniaia V2, Bielfeldt S3.
• J Cosmet Dermatol. 2012 Jun:11(2):87-92. doi: 10.1111/j.1473-2165.2012.00608.x. Hyaluronic acid plus mannitol treatment for improved skin hydration and elasticity. Taieb M1, Gay C, Sebban S, Secnazi P.
• J Cosmet Dermatol. 2014 Dec:13(4):277-87. Anti-aging and filling efficacy of six types hyaluronic acid based dermocosmetic treatment: double blind, randomized clinical trial of efficacy and safety. Nobile V1, Buonocore D, Michelotti A, Marzatico F.
• J Cosmet Dermatol. 2014 Dec:13(4):307-14. doi: 10.1111/jocd.12116. A new dermal filler made of cross-linked and auto-crosslinked hyaluronic acid in the correction of facial aging defects. Sparavigna A1, Fino P, Tenconi B, Giordan N, Amorosi V, Scuderi N.
• Journal of Investigative Dermatology (2010) 130, 1107–1115: Functional MC1R-Gene Variants Are Associated with Increased Risk for Severe Photoaging of Facial Skin: Anissa Elfakir1, Khaled Ezzedine2,3, Julie Latreille1, Laurence Ambroisine1, Randa Jdid4, Pilar Galan2, Serge Hercberg2, Florian Gruber5, Denis Malvy2,6, Erwin Tschachler5,7 and Christiane Guinot
• Journal of Investigative Dermatology (2013) 133, 929–935, A Genome-Wide Association Study in Caucasian Women Points Out a Putative Role of the STXBP5L Gene in Facial Photoaging, Sigrid Le Clerc1,
• Mutat Res. 2005 Apr 1:571(1-2):133-52. MC1R and the response of melanocytes to ultraviolet radiation. Rouzaud F1, Kadekaro AL, Abdel-Malek ZA, Hearing VJ.
• Pathol Biol (Paris). 2015 Feb:63(1):32-34. doi: 10.1016/j.patbio.2014.05.019. Epub 2014 Aug 31. Hyaluronan, a truly “youthful” polysaccharide. Its medical applications. Robert L1.
• Photochem Photobiol. 2011 Sep-Oct:87(5):1105-12. doi: 10.1111/j.1751-1097.2011.00959.x. Epub 2011 Jul 28. Ultraviolet-B irradiation induces differential regulations of hyaluronidase expression and activity in normal human keratinocytes. Kurdykowski S1, Mine S, Bardey V, Danoux L, Jeanmaire C, Pauly G, Brabencova E, Wegrowski Y, Maquart FX.
• Pigment Cell Melanoma Res. 2012 May: 25(3): 384–394. Inherited variants in the MC1R gene and survival from cutaneous melanoma: a BioGenoMEL study, John R Davies,1 Juliette Randerson-Moor,1 Kairen Kukalizch,1 Mark Harland,1 Rajiv Kumar,2 Srinivasan Madhusudan,3 Eduardo Nagore,4 Johan Hansson,5 Veronica Höiom,5 Paola Ghiorzo,6 Nelleke A Gruis,7 Peter A
  Kanetsky,8 Judith Wendt,1,9 Dace Pjanova,10 Susana Puig,11,12 Philippe Saiag,13 Dirk Schadendorf,14 Nadem Soufir,15,16,17 Ichiro Okamoto,9 Paul Affleck,1 Zaida García-Casado,18 Zighereda Ogbah,11,12 Aija Ozola,10 Paola Queirolo,19 Antje Sucker,14 Jennifer H Barrett,1 Remco van Doorn,7 D Timothy Bishop,1 and Julia Newton-Bishop1
• ScientificWorldJournal. 2014:2014:378024. doi: 10.1155/2014/378024. Epub 2014 Oct 14. Dietary hyaluronic acid migrates into the skin of rats. Oe M1, Mitsugi K2, Odanaka W1, Yoshida H1, Matsuoka R1, Seino S1, Kanemitsu T1, Masuda Y1.

Analysed genes:

• GSTT1 (Null Allele)
• GSTM1 (Null Allele)
• GSTP1 (rs1695)
• SOD2 (rs4880)
• GPX1 (rs1050450)

Literature – Genetics:

• Bhatti P et al. Lead exposure, polymorphisms in genes related to oxidative stress, and risk of adult brain tumors. Cancer Epidemiol Biomarkers Prev. 2009 Jun,18(6):1841-8.
• Chen J et al. GPx-1 polymorphism (rs1050450) contributes to tumor susceptibility: evidence from meta-analysis. J Cancer Res Clin Oncol. 2011 Oct,137(10):1553-61.
• Funke S et al. Genetic Polymorphisms in Genes Related to Oxidative Stress (GSTP1, GSTM1, GSTT1, CAT, MnSOD, MPO, eNOS) and Survival of Rectal Cancer Patients after Radiotherapy. Journal of Cancer Epidemiology. Volume 2009 (2009), Article ID 302047.
• Hong Z et al. GPX1 gene Pro200Leu polymorphism, erythrocyte GPX activity, and cancer risk. Mol Biol Rep. 2013 Feb,40(2):1801-12.
• Jablonska E et al. Association between GPx1 Pro198Leu polymorphism, GPx1 activity and plasma selenium concentration in humans. Eur J Nutr. 2009 Sep,48(6):383-6.
• Karunasinghe N et al. Serum selenium and single-nucleotide polymorphisms in genes for selenoproteins: relationship to markers of oxidative stress in men from Auckland, New Zealand. Genes Nutr. 2012 Apr,7(2):179-90.
• Lightfoot TJ et al. Polymorphisms in the oxidative stress genes, superoxide dismutase, glutathione peroxidase and catalase and risk of nonHodgkin’s lymphoma. Haematologica. 2006 Sep,91(9):1222-7.
• Massy ZA et al. The role of oxidative stress in chronic kidney disease. Semin Dial. 2009 Jul-Aug,22(4):405-8.
• McWilliams et al. Glutathione S-transferase M1 (GSTM1) deficiency and lung cancer risk. Cancer Epidemiol Biomarkers Prev 1995,4:589-594.
• Miller et al. An association between glutathione S-transferase P1 gene polymorphism and younger age at onset of lung carcinoma. Cancer. 2006 Oct 1,107(7):1570-7
• Paludo FJ et al. Effects of 47C allele (rs4880) of the SOD2 gene in the production of intracellular reactive species in peripheral blood mononuclear cells with and without lipopolysaccharides induction. Free Radic Res. 2014 Feb,48(2):190-9.
• Pourvali K et al. Role of Superoxide Dismutase 2 Gene Ala16Val Polymorphism and Total Antioxidant Capacity in Diabetes and its Complications. Avicenna J Med Biotechnol. 2016 Apr-Jun,8(2):48-56.
• Soerensen M et al. The Mn-superoxide dismutase single nucleotide polymorphism rs4880 and the glutathione peroxidase 1 single nucleotide polymorphism rs1050450 are associated with aging and longevity in the oldest old. Mech Ageing Dev. 2009 May,130(5):308-14.
• Sreeja L et al. Glutathione S-transferase M1, T1 and P1 polymorphisms: susceptibility and outcome in lung cancer patients. J Exp Ther Oncol. 2008,7(1):73-85
• Stücker et al. Genetic polymorphisms of glutathione S-transferases as modulators of lung cancer susceptibility. Carcinogenesis. 2002 Sep, 23(9):1475-81.
• Sutton A et al. The Ala16Val genetic dimorphism modulates the import of human manganese superoxide dismutase into rat liver mitochondria. Pharmacogenetics. 2003 Mar,13(3):145-57.
• Tang TS et al. Association between the rs1050450 glutathione peroxidase-1 (C > T) gene variant and peripheral neuropathy in two independent samples of subjects with diabetes mellitus. Nutr Metab Cardiovasc Dis. 2012 May,22(5):417-25.
• Xiong YM et al. Association study between polymorphisms in selenoprotein genes and susceptibility to Kashin-Beck disease. Osteoarthritis Cartilage. 2010 Jun,18(6):817-24.
• Zejnilovic J et al. Association between manganese superoxide dismutase polymorphism and risk of lung cancer. Cancer Genet Cytogenet. 2009 Feb,189(1):1-4.

Literature – Action Plan:

• Annals of the New York Academy of Sciences, April 2002, pages 133–166.
• Annu Rev Nutr. 1996;16:33-50. Antioxidants in human health and disease. Halliwell B1.
• Beitner, “Randomized, placebo-controlled, double blind study on the clinical efficacy of a cream containing 5% alphalipoic acid related to photoageing of facial skin,” Br. J. Dermatol., vol. 149, no. 4, pp. 841–849, Oct. 2003.
• Burke, “Interaction of vitamins C and E as better cosmeceuticals,” Dermatol. Ther., vol. 20, no. 5, pp. 314–321, Oct. 2007.
• Chan, “Partners in defense, vitamin E and vitamin C,” Can. J. Physiol. Pharmacol., vol. 71, no. 9, pp. 725–731, Sep. 1993.
• Connect Tissue Res. 2010 Oct;51(5):378-87. α-Lipoic acid induces collagen biosynthesis involving prolyl hydroxylase expression via activation of TGF-β-Smad signaling in human dermal fibroblasts. Tsuji-Naito K, Ishikura S, Akagawa M, Saeki H.
• Dreher, Gabard, Schwindt, and Maibach, “Topical melatonin in combination with vitamins E and C
  protects skin from ultraviolet-induced erythema: a human study in vivo,” Br. J. Dermatol., vol. 139, no. 2, pp. 332–339, Aug. 1998.
• Eberlein-König and Ring, “Relevance of vitamins C and E in cutaneous photoprotection,” Journal of Cosmetic Dermatology, vol. 4, pp. 4-9, 2005.
• Food Funct. 2015 Aug 19. Zinc as a micronutrient and its preventive role of oxidative damage in cells. Kloubert V1, Rink L.
• Funke et al. Genetic Polymorphisms in Genes Related to Oxidative Stress (GSTP1, GSTM1, GSTT1, CAT, MnSOD, MPO, eNOS) and Survival of Rectal Cancer Patients after Radiotherapy. J Cancer Epidemiol. 2009, 2009: 302047
• Gomes and Negrato, “Alpha-lipoic acid as a pleiotropic compound with potential therapeutic use in diabetes and other chronic diseases,” Diabetol. Metab. Syndr., vol. 6, no. 1, p. 80, 2014.
• Han and Nimni, “Transdermal delivery of amino acids and antioxidants enhance collagen synthesis: in vivo and in vitro studies,” Connect. Tissue Res., vol. 46, no. 4–5, pp. 251–257, 2005.
• McWilliams et al. Glutathione S-transferase M1 (GSTM1) deficiency and lung cancer risk. Cancer Epidemiol Biomarkers Prev 1995,4:589-594.
• Miller et al. An association between glutathione S-transferase P1 gene polymorphism and younger age at onset of lung carcinoma. Cancer. 2006 Oct 1,107(7):1570-7.
• Moura, de Andrade, Dos Santos, and Goulart, “Lipoic Acid: its Antioxidant and Anti-Inflammatory
  Role and Clinical Applications,” Curr. Top. Med. Chem., Jan. 2015.
• Murray, Darr, Reich, and Pinnell, “Topical vitamin-C treatment reduces ultraviolet-B radiation-induced erythema in human skin,” in Journal of Investigative Dermatology, 1991, vol. 96, pp. 587–587.
• Murray Michael T (2005) Encyclopedia of Nutritional Supplements, The Essential Guide for Improving Your HealthNaturally, Prima Publishing
• Panich, Tangsupa-a-nan, Onkoksoong, Kongtaphan, Kasetsinsombat, Akarasereenont, and Wongkajornsilp, “Inhibition of UVA-mediated melanogenesis by ascorbic acid through modulation of antioxidant defense and nitric oxide system,” Arch. Pharm. Res., vol. 34, no. 5, pp. 811–820, May 2011.
• Park, Ock, Kim, Park,  Lee, Choi, Cho, Lee, Cho, and Cho, “Vitamin C attenuates ERK signalling to inhibit the regulation of collagen production by LL-37 in human dermal fibroblasts,” Exp. Dermatol., vol. 19, no. 8, pp. e258–e264, Aug. 2010.
• Pedrelli, Lauriola, and Pigatto, “Clinical evaluation of photoprotective effect by a topical antioxidants combination [tocopherols and tocotrienols],” Journal of the European Academy of Dermatology and Venereology, vol. 26, pp. 1449-1453, 2012.
• Petersen Shay, Moreau, Smith, and Hagen, “Is alpha-lipoic acid a scavenger of reactive oxygen species in vivo? Evidence for its initiation of stress signaling pathways that promote endogenous antioxidant capacity,” IUBMB Life, vol. 60, no. 6, pp. 362–367, Jun. 2008.
• Podda, Rallis, Traber, Packer, and Maibach, “Kinetic study of cutaneous and subcutaneous distribution following topical application of [7,8-14C]rac-alpha-lipoic acid onto hairless mice,” Biochem. Pharmacol., vol. 52, no. 4, pp. 627–633, Aug.
• Quevedo, Holstein, Dyckman, and McDonald, “The responses of the human epidermal melanocyte
  system to chronic erythemal doses of UVR in skin protected by topical applications of a combination of vitamins C and E,” Pigment Cell Res. Spons. Eur. Soc. Pigment Cell Res. Int. Pigment Cell Soc., vol. 13, no. 3, pp. 190–192, Jun. 2000.
• Raschke, Koop, Düsing, Filbry, Sauermann, Jaspers, Wenck, and Wittern, “Topical activity of
  ascorbic acid: from in vitro optimization to in vivo efficacy,” Skin Pharmacol. Physiol., vol. 17, no. 4, pp. 200–206, Aug. 2004.
• Sherif, Bendas, and Badawy, “The clinical efficacy of cosmeceutical application of liquid crystalline
  nanostructured dispersions of alpha lipoic acid as anti-wrinkle,” Eur. J. Pharm. Biopharm. Off. J. Arbeitsgemeinschaft Für Pharm. Verfahrenstechnik EV, vol. 86, no. 2, pp. 251–259, Feb. 2014.
• Sreeja et al. Glutathione S-transferase M1, T1 and P1 polymorphisms: susceptibility and outcome in lung cancer patients. J Exp Ther Oncol. 2008,7(1):73-85.
• Stamford, “Stability, transdermal penetration, and cutaneous effects of ascorbic acid and its derivatives,” J. Cosmet. Dermatol., vol. 11, no. 4, pp. 310–317, Dec. 2012.
• Stücker et al. Genetic polymorphisms of glutathione S-transferases as modulators of lung cancer susceptibility. Carcinogenesis. 2002 Sep, 23(9):1475-8
• Sutton et al. The manganese superoxide dismutase Ala16Val dimorphism modulates both mitochondrial import and mRNA stability. Pharmacogenet Genomics. 2005 May,15(5):311-9
• Tavakkol, Nabi, Soliman, and Polefka, “Delivery of vitamin E to the skin by a novel liquid skin cleanser: Comparison of topical versus oral supplementation,” J. Cosmet. Sci., vol. 55, pp.177-187, March 2004.
• Thiele, Hsieh, and Ekanayake-Mudiyanselage, “Vitamin E: Critical Review of Its Current Use in Cosmetic and Clinical Dermatology,” Dermatol Surg,vol. 31, pp. 805-813, 2005.

Analysed genes:

• NQO1 (rs1800566) 

Literature – Genetics:

• Fischer A et al. Association between genetic variants in the Coenzyme Q10 metabolism and Coenzyme Q10 status in humans. BMC Res Notes. 2011 Jul 21,4:245.
• Freriksen JJ et al. Genetic polymorphism 609C>T in NAD(P)H:quinone oxidoreductase 1 enhances the risk of proximal colon cancer. J Hum Genet. 2014 Jul,59(7):381-6.
• Lajin B et al. he NQO1 polymorphism C609T (Pro187Ser) and cancer susceptibility: a comprehensive meta-analysis. Br J Cancer. 2013 Sep 3,109(5):1325-37.
• Ross D et al. NAD(P)H:quinone oxidoreductase 1 (NQO1): chemoprotection, bioactivation, gene regulation and genetic polymorphisms. Chem Biol Interact. 2000 Dec 1,129(1-2):77-97.
• Zhang J et al. Detection of quinone oxidoreductase 1 (NQO1) single-nucleotide polymorphisms (SNP) related to benzene metabolism in immortalized B lymphocytes from a Chinese Han population. J Toxicol Environ Health A. 2010,73(7):490-8.

Literature – Action Plan:

• Brugè, Damiani, Puglia, Offerta, Armeni, Littarru, and Tiano, “Nanostructured lipid carriers loaded
  with CoQ10: effect on human dermal fibroblasts under normal and UVA-mediated oxidative conditions,” Int. J. Pharm., vol. 455, no. 1–2, pp. 348–356, Oct. 2013.
• Choi, H. S. Song, H. R. Kim, T. W. Park, T. D. Kim, B. J. Cho, C. J. Kim, and S. S. Sim, “Effect of coenzyme Q10 on cutaneous healing in skin-incised mice,” Arch. Pharm. Res., vol. 32, no. 6, pp. 907–913, Jun. 2009.
• Fasano, Serini, Mondella, Trombino, Celleno, Lanza, Cittadini, and Calviello, “Antioxidant and Anti-Inflammatory Effects of Selected Natural Compounds Contained in a Dietary Supplement on Two Human Immortalized Keratinocyte Lines,” BioMed Res. Int., vol. 2014, pp. 1–11, 2014.
• Fischer et al. Association between genetic variants in the Coenzyme Q10 metabolism and Coenzyme Q10 status in humans. Published online Jul 21, 2011.
• Freriksen et al. Genetic polymorphism 609C>T in NAD(P)H:quinone oxidoreductase 1 enhances the risk of proximal colon cancer. J Hum Genet. 2014 May
• Fuller, Smith, Howerton, and Kern, “Anti-inflammatory effects of CoQ10 and colorless carotenoids,” J. Cosmet. Dermatol., vol. 5, no. 1, pp. 30–38, Mar. 2006.
• Garrido-Maraver, Cordero, Oropesa-Ávila, Fernández Vega, de la Mata, Delgado Pavón, de Miguel, Pérez Calero, Villanueva Paz, Cotán, and Sánchez-Alcázar, “Coenzyme Q10 Therapy,” Mol. Syndromol., vol. 5, no. 3–4, pp. 187–197, Jul. 2014.
• Grether-Beck, Marini, Jaenicke, and Krutmann, “Effective Photoprotection of Human Skin against Infrared A Radiation by Topically Applied Antioxidants: Results from a Vehicle Controlled, Double-Blind, Randomized Study,” Photochem. Photobiol., vol. 91, no. 1, pp. 248–250, Jan. 2015.
• Hoppe, J. Bergemann, W. Diembeck, J. Ennen, S. Gohla, I. Harris, J. Jacob, J. Kielholz, W. Mei, D. Pollet, D. Schachtschabel, G. Sauermann, V. Schreiner, F. Stäb, and F. Steckel, “Coenzyme Q10, a cutaneous antioxidant and energizer,” BioFactors Oxf. Engl., vol. 9, no. 2–4, pp. 371–378, 1999
• Inui, Ooe, Fujii, Matsunaka, Yoshida, and Ichihashi, “Mechanisms of inhibitory effects of CoQ10 on UVBinduced wrinkle formation in vitro and in vivo,” BioFactors Oxf. Engl., vol. 32, no. 1–4, pp. 237–243, 2008.
• Littarru and Tiano, “Bioenergetic and antioxidant properties of coenzyme Q10: recent developments,” Mol. Biotechnol., vol. 37, no. 1, pp. 31–37, Sep. 2007.
• Lohan, S. Bauersachs, S. Ahlberg, N. Baisaeng, C. M. Keck, R. H. Müller, E. Witte, K. Wolk, S. Hackbarth, B. Röder, J. Lademann, and M. C. Meinke, “Ultra-small lipid nanoparticles promote the penetration of coenzyme Q10 in skin cells and counteract oxidative stress,” Eur. J. Pharm. Biopharm. Off. J. Arbeitsgemeinschaft Pharm. Verfahrenstechnik EV, Dec. 2014.
• Mohr D et al. Dietary supplementation with coenzyme Q10 results in increased levels of ubiquinol-10 within circulating lipoproteins and increased resistance of human low-density lipoprotein to the initiation of lipid peroxidation. Biochim Biophys Acta. 1992 Jun 26;1126(3):247-54.
• Muta-Takada, Terada, Yamanishi, Ashida, Inomata, Nishiyama, and Amano, “Coenzyme Q10 protects against oxidative stress-induced cell death and enhances the synthesis of basement membrane components in dermal and epidermal cells,”BioFactors Oxf. Engl., vol. 35, no. 5, pp. 435–441, Oct. 2009.
• Rona, Vailati, and Berardesca, “The cosmetic treatment of wrinkles,” J. Cosmet. Dermatol., vol. 3, no. 1, pp. 26–34, Jan. 2004.
• Ross D et al. NAD(P)H:quinone oxidoreductase 1 (NQO1): chemoprotection, bioactivation, gene regulation and genetic polymorphisms. Chem Biol Interact. 2000 Dec 1;129(1-2):77-97.
• Winkler-Stuck, Wiedemann, Wallesch, and Kunz, “Effect of coenzyme Q10 on the mitochondrial
  function of skin fibroblasts from Parkinson patients,” J. Neurol. Sci., vol. 220, no. 1–2, pp. 41–48, May 2004.
• Yue, Zhou, Liu, Li, Yan, and Duan, “The advantages of a novel CoQ10 delivery system in skin photoprotection,”Int. J. Pharm., vol. 392, no. 1–2, pp. 57–63, Jun. 2010.
• Zhang, Dang, Guo, Wang, Zhao, and Zhao, “Coenzyme Q(10) enhances dermal elastin expression, inhibits IL-1α production and melanin synthesis in vitro,” Int. J. Cosmet. Sci., vol. 34, no. 3, pp. 273–279, Jun. 2012.

Analysed genes:

• GPX1 (rs1050450)

Literature – Genetics:

• Bhatti P et al. Lead exposure, polymorphisms in genes related to oxidative stress, and risk of adult brain tumors. Cancer Epidemiol Biomarkers Prev. 2009 Jun,18(6):1841-8.
• Chen J et al. GPx-1 polymorphism (rs1050450) contributes to tumor susceptibility: evidence from meta-analysis. J Cancer Res Clin Oncol. 2011 Oct,137(10):1553-61.
• Hong Z et al. GPX1 gene Pro200Leu polymorphism, erythrocyte GPX activity, and cancer risk. Mol Biol Rep. 2013 Feb,40(2):1801-12.
• Hu YJ et al. Role of glutathione peroxidase 1 in breast cancer: loss of heterozygosity and allelic differences in the response to selenium. Cancer Res. 2003 Jun 15,63(12):3347-51.
• Jablonska E et al. Association between GPx1 Pro198Leu polymorphism, GPx1 activity and plasma selenium concentration in humans. Eur J Nutr. 2009 Sep,48(6):383-6.
• Karunasinghe N et al. Serum selenium and single-nucleotide polymorphisms in genes for selenoproteins: relationship to markers of oxidative stress in men from Auckland, New Zealand. Genes Nutr. 2012 Apr,7(2):179-90.
• Tang TS et al. Association between the rs1050450 glutathione peroxidase-1 (C > T) gene variant and peripheral neuropathy in two independent samples of subjects with diabetes mellitus. Nutr Metab Cardiovasc Dis. 2012 May,22(5):417-25.
• Xiong YM et al. Association study between polymorphisms in selenoprotein genes and susceptibility to Kashin-Beck disease. Osteoarthritis Cartilage. 2010 Jun,18(6):817-24.

Literature – Action Plan:

• Bhatti et al. Lead exposure, polymorphisms in genes related to oxidative stress and risk of adult brain tumors. Cancer Epidemiol Biomarkers Prev. Jun 2009, 18(6):1841–1848.
• Chen et al. GPx-1 polymorphism (rs1050450) contributes to tumor susceptibility: evidence from meta-analysis. J Cancer Res Clin Oncol. 2011 Oct,137(10):1553-61.
• Hong et al. GPX1 gene Pro200Leu polymorphism, erythrocyte GPX activity, and cancer risk. Mol Biol Rep. 2013 Feb,40(2):1801-12.
• Jablonska E et al. Association between GPx1 Pro198Leu polymorphism, GPx1 activity and plasma selenium concentration in humans. Eur J Nutr. 2009 Sep,48(6):
• Karunasinghe et al. Serum selenium and single-nucleotide polymorphisms in genes for selenoproteins: relationship to markers of oxidative stress in men from Auckland, New Zealand. Genes Nutr. 2012 Apr,7(2):179-90.
• Soerensen et al. The Mn-superoxide dismutase single nucleotide polymorphism rs4880 and the glutathione peroxidase 1 single nucleotide polymorphism rs1050450 are associated with aging and longevity in the oldest old. Mech Ageing Dev. 2009 May,130(5):308-14.
• Steinbrecher et al. Effects of selenium status and polymorphisms in selenoprotein genes on prostate cancer risk in a prospective study of European men. Cancer Epidemiol Biomarkers Prev. 2010 Nov,19(11):2958-68.
• Tang et al. Association between the rs1050450 glutathione peroxidase-1 (C > T) gene variant and peripheral neuropathy in two independent samples of subjects with diabetes mellitus. Nutr Metab Cardiovasc Dis. 2012 May,22(5):417-25.
• Xiong et al. Association study between polymorphisms in selenoprotein genes and susceptibility to Kashin-Beck disease. Osteoarthritis Cartilage. 2010 Jun,18(6):817-24.

Analysed genes:

• IL1RN (rs419598)
• IL1A (rs1800587)
• IL1B (rs1143634)
• TNF-α (rs1800629) 

Literature – Genetics:

• Baradaran-Rahimi et al. Association of interleukin-1 receptor antagonist gene polymorphisms with generalized aggressive periodontitis in an Iranian population. J Periodontol. 2010 Sep,81(9):1342-6.
• Buchs N et al. IL-1B and IL-1Ra gene polymorphisms and disease severity in rheumatoid arthritis: interaction with their plasma levels. Genes Immun. 2001 Jun,2(4):222-8.
• Burada F et al. IL-1RN +2018T>C polymorphism is correlated with colorectal cancer. Mol Biol Rep. 2013 Apr,40(4):2851-7.
• Dominici R et al. Cloning and functional analysis of the allelic polymorphism in the transcription regulatory region of interleukin-1 alpha. Immunogenetics. 2002 May,54(2):82-6. Epub 2002 Mar 19.
• E Louis et al. Tumour necrosis factor (TNF) gene polymorphism influences TNF-α production in lipopolysaccharide (LPS)-stimulated whole blood cell culture in healthy humans. Clin Exp Immunol. 1998 Sep, 113(3): 401–406.
• Ferreira AC et al. NOD2/CARD15 and TNFA, but not IL1B and IL1RN, are associated with Crohn’s disease. Inflamm Bowel Dis. 2005 Apr,11(4):331-9.
• Gore et al. Interleukin-1beta+3953 allele 2: association with disease status in adult periodontitis. J Clin Periodontol. 1998 Oct,25(10):781-5.
• Int J Oral Maxillofac Surg. 2013 Apr,42(4):537-43. doi: 10.1016/j.ijom.2012.07.018. Epub 2012 Aug 24. Genetic and immunological markers predict titanium implant failure: a retrospective study. Jacobi-Gresser E1, Huesker K, Schütt S.
• Lakka HM et al. The TNF-alpha G-308A polymorphism is associated with C-reactive protein levels: the HERITAGE Family Study. Vascul Pharmacol. 2006 May,44(5):377-83.
• Moen A et al. Role of IL1A rs1800587, IL1B rs1143627 and IL1RN rs2234677 genotype regarding development of chronic lumbar radicular pain, a prospective one-year study. PLoS One. 2014 Sep 10,9(9):e107301.
• Mwantembe O et al. Ethnic differences in allelic associations of the interleukin-1 gene cluster in South African patients with inflammatory bowel disease (IBD) and in control individuals. Immunogenetics. 2001,52(3-4):249-54.
• Nikolopoulos GK et al. Cytokine gene polymorphisms in periodontal disease: a metaanalysis of 53 studies including 4178 cases and 4590 controls. J Clin Periodontol 2008, 35: 754–767
• Trevilatto et al. Association of IL1 gene polymorphisms with chronic periodontitis in Brazilians. Arch Oral Biol. 2011 Jan,56(1):54-62.
• Victor Menezo et al. Cytokine gene polymorphisms involved in chronicity and complications of anterior uveitis. Cytokine. 2006 Aug,35(3-4):200-6. Epub 2006 Sep 26.
• Vijgen L et al. Interleukin-1 receptor antagonist VNTR-polymorphism in inflammatory bowel disease. Genes Immun. 2002 Nov,3(7):400-6.
• Yin WT et al. Association between IL-1α rs17561 and IL-1β rs1143634 polymorphisms and periodontitis: a meta-analysis. Genet Mol Res. 2016 Feb 5,15(1)
• Yong-Hui Yang et al. Genetic polymorphisms of the TNF-α-308G/A are associated with metabolic syndrome in asthmatic patients from Hebei province, China. Int J Clin Exp Pathol. 2015,,8(10): 13739–13746

Literature – Action Plan:

• Cell Mol Biol (Noisy-le-grand). 2011 Feb 12:57(1):62-9. Effect of topical application of methylsulfonylmethane (MSM), EDTA on pitting edema and oxidative stress in a double blind, placebo-controlled study. Tripathi R1, Gupta S, Rai S, Mittal PC.
• Cytokine. 2015 Feb:71(2):223-31. Methylsulfonylmethane inhibits NLRP3 inflammasome activation. Ahn H1, Kim J1, Lee MJ1, Kim YJ2, Cho YW3, Lee GS4.
• Dayer et al. The pivotal role of interleukin-1 in the clinical manifestations of rheumatoid arthritis. Rheumatology 2003,42(Suppl. 2):ii3–ii10
• Drug Deliv. 2009 Jul:16(5):243-8. doi: 10.1080/10717540902896362. Assessment of methylsulfonylmethane as a permeability enhancer for regional EDTA chelation therapy. Zhang M1, Wong IG, Gin JB, Ansari NH.
• Goldring et al. Pathogenesis of bone and cartilage destruction in rheumatoid arthritis. Rheumatology 2003,42(Suppl. 2):ii11–ii16
• Hruza LL, Pentland AP. Mechanisms of UV-induced inflammation. J Invest Dermatol. 1993:100:35S-41S.
• Oregón-Romero et al. Tumor necrosis factor alpha-308 and -238 polymorphisms in rheumatoid arthritis. Association with messenger RNA expression and sTNF-alpha. J Investig Med. 2008 Oct,56(7):937-4
• Osteoarthritis Cartilage. 2008 Nov:16(11):1277-88. doi: 10.1016/j.joca.2008.03.002. Epub 2008 Apr 15. Systematic review of the nutritional supplements dimethyl sulfoxide (DMSO) and methylsulfonylmethane (MSM) in the treatment of osteoarthritis. Brien S1, Prescott P, Bashir N, Lewith H, Lewith G.
• Virtanen et al. Occupational and genetic risk factors associated with intervertebral disc disease. Spine (Phila Pa 1976). 2007 May 1,32(10):1129-34.

Analysed genes:

• TERT (rs2242652)
• TERT (rs2735940)
• BICD1 (rs2630578)
• PPARG (rs1801282)

Literature – Genetics:

• Bojesen SE et al. Multiple independent variants at the TERT locus are associated with telomere length and risks of breast and ovarian cancer. Nat Genet. 2013 Apr,45(4):371-84, 384e1-2.
• Campa D et al. Risk of multiple myeloma is associated with polymorphisms within telomerase genes and telomere length. Int J Cancer. 2015 Mar 1,136(5):E351-8.
• Fitó M et al. Nutritional Genomics and the Mediterranean Diet’s Effects on Human Cardiovascular Health. Nutrients. 2016 Apr 13,8(4):218.
• García-Calzón S et al. Pro12Ala polymorphism of the PPARγ2 gene interacts with a mediterranean diet to prevent telomere shortening in the PREDIMED-NAVARRA randomized trial. Circ Cardiovasc Genet. 2015 Feb,8(1):91-9.
• Ludlow AT et al. Relationship between physical activity level, telomere length, and telomerase activity. Med Sci Sports Exerc. 2008 Oct,40(10):1764-71.
• Mangino M et al. A regulatory SNP of the BICD1 gene contributes to telomere length variation in humans. Hum Mol Genet. 2008 Aug 15,17(16):2518-23.
• Matsubara Y et al. Telomere length of normal leukocytes is affected by a functional polymorphism of hTERT. Biochem Biophys Res Commun. 2006 Mar 3,341(1):128-31.
• Matsubara Y et al. Coronary artery disease and a functional polymorphism of hTERT. Biochem Biophys Res Commun. 2006 Sep 22,348(2):669-72.
• Pellatt AJ et al. Genetic and lifestyle influence on telomere length and subsequent risk of colon cancer in a case control study. Int J Mol Epidemiol Genet. 2012,3(3):184-94.
• Sheng X et al. TERT polymorphisms modify the risk of acute lymphoblastic leukemia in Chinese children. Carcinogenesis. 2013 Jan,34(1):228-35.

Literature – Action Plan:

• Arshad H. Rahmani et al. Implications of Green Tea and Its Constituents in the Prevention of Cancer via the Modulation of Cell Signalling Pathway. Biomed Res Int. 2015; 2015: 925640.
• Artandi S.E., DePinho R.A. Telomeres and telomerase in cancer. Carcinogenesis. 2010:31:9–18.
• Brahma N. Singh et al. Green tea catechin, epigallocatechin-3-gallate (EGCG): mechanisms, perspectives and clinical applications. Biochem Pharmacol. 2011 Dec 15; 82(12): 1807–1821.
• Cancer Res, Chemoprevention of human prostate cancer by oral administration of green tea catechins in volunteers with high-grade prostate intraepithelial neoplasia: a preliminary report from a one-year proof-of-principle study. . 2006 Jan 15;66(2):1234-40.
• Carcinogenesis. 2013 Jan:34(1):228-35. TERT polymorphisms modify the risk of acute lymphoblastic leukemia in Chinese children. Sheng X1, Tong N, Tao G, Luo D, Wang M, Fang Y, Li J, Xu M, Zhang Z, Wu D.
• Cells. 2013 Mar: 2(1): 57–66. Functional Assessment of Pharmacological Telomerase Activators in Human T cells. Brenda Molgora,1 Riley Bateman,1 Greg Sweeney,1 Danielle Finger,1 Taylor Dimler,1 Rita B. Effros,2 and Hector F. Valenzuela1,
• Circ Cardiovasc Genet. 2015 Feb:8(1):91-9. Pro12Ala polymorphism of the PPARγ2 gene interacts with a mediterranean diet to prevent telomere shortening in the PREDIMED-NAVARRA randomized trial. García-Calzón S1, Martínez-González MA1, Razquin C1, Corella D1, Salas Salvadó J1, Martínez JA1, Zalba G1, Marti A2.
• Cochrane Database of Systematic Reviews 2009, Issue 3. Art. No.: CD005004: Green tea (Camellia sinensis) for the prevention of cancer. 
• de Jesus B.B., Schneeberger K., Vera E., Tejera A., Harley C.B., Blasco M.A. The telomerase activator TA-65 elongates short telomeres and increases health span of adult/old mice without increasing cancer incidence. Aging Cell. 2011:10:604–621.
• de Lange T. Shelterin: The protein complex that shapes and safeguards human telomeres. Gene Dev.2005:19:2100–2110.
• Dermatology. 2002:204(3):214-21. Safety and efficacy of combined high-dose treatment with calcipotriol ointment and solution in patients with psoriasis. Van de Kerkhof PC1, Green C, Hamberg KJ, Hutchinson PE, Jensen JK, Kidson P, Kragballe K, Larsen FG, Munro CS, Tillman DM.
• Dong XX et al. Ginkgo biloba extract reduces endothelial progenitor-cell senescence through augmentation of telomerase activity. J Cardiovasc Pharmacol. 2007 Feb;49(2):111-5.
• Eur J Cancer Prev, Protective effects of green tea extracts (polyphenon E and EGCG) on human cervical lesions. 2003 Oct;12(5):383-90.
• Genes Chromosomes Cancer. 2013 Jul:52(7):595-609.Telomere length, telomere-related genes, and breast cancer risk: the breast cancer health disparities study. Pellatt AJ1, Wolff RK, Torres-Mejia G, John EM, Herrick JS, Lundgreen A, Baumgartner KB, Giuliano AR, Hines LM, Fejerman L, Cawthon R, Slattery ML.
• Hiyama K., Hirai Y., Kyoizumi S., Akiyama M., Hiyama E., Piatyszek M.A., Shay J.W., Ishioka S., Yamakido M. Activation of telomerase in human lymphocytes and hematopoietic progenitor cells. J. Immunol. 1995:155:3711–3715
• Hum Genet. 2011 Mar:129(3):247-53. Genetic variants in telomere-maintaining genes and skin cancer risk. Nan H1, Qureshi AA, Prescott J, De Vivo I, Han J.
• Hum Mol Genet. 2008 Aug 15:17(16):2518-23. A regulatory SNP of the BICD1 gene contributes to telomere length variation in humans. Mangino M1, Brouilette S, Braund P, Tirmizi N, Vasa-Nicotera M, Thompson JR, Samani NJ.
• Int J Cancer. 2015 Mar 1:136(5):E351-8. Risk of multiple myeloma is associated with polymorphisms within telomerase genes and telomere length. Campa D1, Martino A, Varkonyi J, Lesueur F, Jamroziak K, Landi S, Jurczyszyn A, Marques H, Andersen V, Jurado M, Brenner H, Petrini M, Vogel U, García-Sanz R, Buda G, Gemignani F, Ríos R, Vangsted
  AJ, Dumontet C, Martínez-López J, Moreno MJ, Stępień A, Wątek M, Moreno V, Dieffenbach AK, Rossi AM,Butterbach K, Jacobsen SE, Goldschmidt H, Sainz J, Hillengass J, Orciuolo E, Dudziński M, Weinhold N, Reis RM, Canzian F.
• Int J Mol Epidemiol Genet. 2012: 3(3): 184–194. Genetic and lifestyle influence on telomere length and subsequent risk of colon cancer in a case control study. Andrew J Pellatt,1 Roger K Wolff,1 Abbie Lundgreen,1 Richard Cawthon,2 and Martha L Slattery1
• Int J Obes (Lond). 2012 Jun:36(6):805-9. doi: 10.1038/ijo.2011.197. Epub 2011 Oct 11. Increased telomerase activity and vitamin D supplementation in overweight African Americans. Zhu H1, Guo D, Li K, Pedersen-White J, Stallmann-Jorgensen IS, Huang Y, Parikh S, Liu K, Dong Y.
• Jäger K et al. Therapeutic Targeting of Telomerase. Genes (Basel). 2016 Jul 21;7(7).
• Jaskelioff M., Muller F.L., Paik J.H., Thomas E., Jiang S., Adams A.C., Sahin E., Kost-Alimova M., Protopopov A., Cadinanos J., et al. Telomerase reactivation reverses tissue degeneration in aged telomerase-deficient mice. Nature. 2011:469:102–106.
• J Mol Med (Berl). 2012 Sep:90(9):1059-67. Genetic variants implicated in telomere length associated with left ventricular function in patients with hypertension and cardiac organ damage. Huber M1, Treszl A, Wehland M, Winther I, Zergibel I, Reibis R, Bolbrinker J, Stoll M, Schönfelder G, Wegscheider K, Völler H, Kreutz R.
• L Xia et al. Resveratrol reduces endothelial progenitor cells senescence through augmentation of telomerase activity by Akt-dependent mechanisms. Br J Pharmacol. 2008 Oct; 155(3): 387–394.
• Molecules. 2014 Sep 17:19(9):14794-808. Enhanced antioxidant capacity and anti-ageing biomarkers after diet micronutrient supplementation. Balcerczyk A1, Gajewska A1, Macierzyńska-Piotrowska E1, Pawelczyk T2, Bartosz G1, Szemraj J3
• Monteiro J., Batliwalla F., Ostrer H., Gregersen P.K. Shortened telomeres in clonally expanded CD28-CD8+ T cells imply a replicative history that is distinct from their CD28+CD8+ counterparts. J. Immunol.1996:156:3587–3590
• Naasani I et al. Telomerase inhibition, telomere shortening, and senescence of cancer cells by tea catechins. Biochem Biophys Res Commun. 1998 Aug 19;249(2):391-6.
• Nat Genet. 2013 Apr: 45(4): 371–384e2. Multiple independent variants at the TERT locus are associated with telomere length and risks of breast and ovarian cancer. Stig E Bojesen et al.
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