title: Human Pigmentation, Cutaneous Vitamin D Synthesis and Evolution: Variants of Genes (SNPs) Involved in Skin Pigmentation Are Associated with 25(OH)D Serum Concentration.
abstract: Vitamin D deficiency is common and associated with higher risk for and unfavourable outcome of many diseases. Limited data exist on genetic determinants of serum 25(OH)D concentration. In a cohort of the LURIC study (n=2974, median 25(OH)D concentration 15.5 ng/ml), we tested the hypothesis that variants (SNPs, n=244) of several genes (n=15) involved in different aspects of skin pigmentation, including melanosomal biogenesis (ATP7A, DTNBP1, BLOC1S5, PLDN, PMEL), melanosomal transport within melanocytes (RAB27A, MYO5A, MLPH); or various melanocyte signaling pathways (MC1R, MITF, PAX3, SOX10, DKK1, RACK1, CNR1) are predictive of serum 25(OH)D levels. Eleven SNPs located in 6 genes were associated (p<0.05) with low or high serum 25(OH)D levels, 3 out of these 11 SNPs reached the aimed significance level after correction for multiple comparisons (FDR). In the linear regression model adjusted for sex, body mass index (BMI), year of birth and month of blood sample rs7565264 (MLPH), rs10932949 (PAX3), and rs9328451 (BLOC1S5) showed a significant association with 25(OH)D. The combined impact on variation of 25(OH)D serum levels (coefficient of determination (R(2))) for the 11 SNPs was 1.6% and for the 3 SNPs after FDR 0.3%. In Cox Regression we identified rs2292881 (MLPH) as having a significant association (advantage) with overall survival. Kaplan-Meier analysis did not show any significant impact of individual SNPs on overall survival. In conclusion, these results shed new light on the role of sunlight, skin pigmentation and vitamin D for human evolution.
authors.affiliation: Department of Dermatology, The Saarland University Hospital, Homburg, Germany.
authors.forename: Willi
authors.initials: W
authors.lastname: Rossberg
authors.affiliation: Department of Dermatology, The Saarland University Hospital, Homburg, Germany.
authors.forename: Roman
authors.initials: R
authors.lastname: Saternus
authors.affiliation: Institute for Medical Biometry, Epidemiology and Medical Informatics, Saarland University, Campus Homburg, Homburg, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Wagenpfeil
authors.affiliation: Vth Department of Medicine (Nephrology, Hypertensiology, Endocrinology, Diabetology, Rheumatology), Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
authors.forename: Marcus
authors.initials: M
authors.lastname: Kleber
authors.affiliation: Vth Department of Medicine (Nephrology, Hypertensiology, Endocrinology, Diabetology, Rheumatology), Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany Synlab Academy, Synlab Services GmbH, Mannheim and Augsburg, Germany Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Graz, Austria.
authors.forename: Winfried
authors.initials: W
authors.lastname: März
authors.affiliation: Department of Dermatology, The Saarland University Hospital, Homburg, Germany.
authors.forename: Sandra
authors.initials: S
authors.lastname: Reichrath
authors.affiliation: Department of Dermatology, The Saarland University Hospital, Homburg, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Vogt
authors.affiliation: Department of Dermatology, The Saarland University Hospital, Homburg, Germany Joerg.reichrath@uks.eu.
authors.forename: Jörg
authors.initials: J
authors.lastname: Reichrath
mesh_terms: D015992:Body Mass Index; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008544:Melanocytes / Q000378:metabolism; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012880:Skin Pigmentation / Q000235:genetics*; D013472:Sunlight; D014807:Vitamin D / Q000031:analogs & derivatives* / Q000096:biosynthesis* / Q000097:blood; D014808:Vitamin D Deficiency / Q000097:blood / Q000235:genetics
chemical_list: D014807:Vitamin D; C104450:25-hydroxyvitamin D
keywords: Human pigmentation; SNPs; melanocytes; sunlight; vitamin D