A closer look at evolution: Variants (SNPs) of genes involved in skin pigmentation, including exoc2, tyr, tyrp1, and dct, are associated with 25(oh)d serum concentration

Abstract

VitaminDdeficiency iscommonin the Caucasian populationandis associated with increased incidence and unfavorable outcome of many diseases, including various types of cancer, infectious, cardiovascular, andautoimmunediseases. Individual factors that predispose for a person's vitaminDstatus, such as skin type, have been identified, but limited data exist on genetic determinants of serum 25-hydroxyvitaminD(25[OH]D) concentration.Wehave tested the hypothesis that variants of genes (single nucleotide polymorphisms [SNPs]) involved in skin pigmentation are predictive of serum 25(OH)D levels. Serum 25(OH)D and SNPs (n = 960) related to genes with relevance for skin pigmentation (tyrosinase [TYR], TYR-related protein 1 [TYRP1], dopachrome tautomerase [DCT], oculocutaneous albinism II [OCA2], two pore segment channel 2 [TPCN2], solute carrier family 24 A4 [SLC24A4], solute carrier family 45 A2 [SLC45A2], agouti signalling peptide [ASIP], cyclic AMP-dependent transcription factor [ATF1], microphthalmia-Associated transcription factor [MITF], proopiomelanocortin [POMC], cAMP-dependent protein kinase catalytic subunit beta [PRKACB], cAMP-dependent protein kinase catalytic subunit gamma [PRKACG], cAMP-dependent protein kinase type I-Alpha regulatory subunit [PRKAR1A], cAMP-dependent protein kinase type II-Alpha regulatory subunit [PRKAR2A], cAMP-dependent protein kinase type II-beta regulatory subunit [PRKAR2B], tubulin beta-3 chain/melanocortin receptor 1 [TUBB3/MC1R], Cadherin-1 [CDH1], catenin beta 1 [CTNNB1], Endothelin 1 [EDN1], endothelin 3 [EDN3], endothelin receptor type B [EDNRB], fibroblast growth factor 2 [FGF2], KIT, KIT ligand [KITLG], nerve growth factor [NGF], interferon regulatory factor 4 [IRF4], exocyst complex component 2[EXOC2],andtumor protein 53 [TP53]) were analyzed in a cohort of participants of the Ludwigshafen Risk and Cardiovascular Health Study (n = 2970).Atotal of 46 SNPs were associated (P