Common genetic variations in the CYP2R1 and GC genes are determinants of vitamin D status in Danes

Environmental factors such as diet, intake of vitamin D supplements and exposure to sunlight are known to influence serumvitamin D concentrations. Genetic epidemiology of vitamin D is in its infancy and a better understanding on how geneticvariation influences vitamin D concentration is needed. We aimed to analyse previously reported vitamin D-relatedpolymorphisms in relation to serum 25(OH)D concentrations in 201 healthy Danish families with dependent children in latesummer in Denmark. Serum 25(OH)D concentrations and a total of 25 SNPs in GC, VDR, CYP2R1, CYP24A1, CYP27B1, C10or88and DHCR7/NADSYN1 genes were analysed in 758 participants. Genotype distributions were in Hardy–Weinberg equilibriumfor the adult population for all the studied polymorphisms. Four SNPs in CYP2R1 (rs1562902, rs7116978, rs10741657 andrs10766197) and six SNPs in GC (rs4588, rs842999, rs2282679, rs12512631, rs16846876 and rs17467825) were statisticallysignificantly associated with serum 25(OH)D concentrations in children, adults and all combined. Several of the SNPs were instrong linkage disequilibrium, and the associations were driven by CYP2R1-rs10741657 and rs10766197, and by GC-rs4588and rs842999. Genetic risk score analysis showed that carriers with no risk alleles of CYP2R1-rs10741657 and rs10766197,and/or GC rs4588 and rs842999 had significantly higher serum 25(OH)D concentrations compared to carriers of all riskalleles. To conclude, our results provide supporting evidence that common polymorphisms in GC and CYP2R1 are associatedwith serum 25(OH)D concentrations in the Caucasian population and that certain haplotypes may predispose to lower25(OH)D concentrations in late summer in Denmark. Citation: Nissen J, Rasmussen LB, Ravn-Haren G, Andersen EW, Hansen B, et al. (2014) Common Variants in CYP2R1 and GC Genes Predict Vitamin DConcentrations in Healthy Danish Children and Adults. PLoS ONE 9(2): e89907. doi:10.1371/journal.pone.0089907 Editor: Nathan A. Ellis, University of Illinois at Chicago, United States of America Received September 25, 2013; Accepted January 23, 2014; Published February 27, 2014 Copyright: ! 2014 Nissen et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permitsunrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Funding: The work was supported by grants from the Danish Dairy Research Fund, Centre for Advanced Food Studies, and The European Region DevelopmentFund. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Competing Interests: The authors have declared that no competing interests exist. * E-mail: [email protected]