Journal article
Common Variants in CYP2R1 and GC Genes Predict Vitamin D Concentrations in Healthy Danish Children and Adults
National Food Institute, Technical University of Denmark1
Division of Nutrition, National Food Institute, Technical University of Denmark2
Division of Toxicology and Risk Assessment, National Food Institute, Technical University of Denmark3
Department of Applied Mathematics and Computer Science, Technical University of Denmark4
Statistics and Data Analysis, Department of Applied Mathematics and Computer Science, Technical University of Denmark5
Aarhus University6
National Research Centre for the Working Environment7
Environmental factors such as diet, intake of vitamin D supplements and exposure to sunlight are known to influence serum vitamin D concentrations. Genetic epidemiology of vitamin D is in its infancy and a better understanding on how genetic variation influences vitamin D concentration is needed. We aimed to analyse previously reported vitamin D-related polymorphisms in relation to serum 25(OH)D concentrations in 201 healthy Danish families with dependent children in late summer in Denmark.
Serum 25(OH)D concentrations and a total of 25 SNPs in GC, VDR, CYP2R1, CYP24A1, CYP27B1, C10or88 and DHCR7/NADSYN1 genes were analysed in 758 participants. Genotype distributions were in Hardy-Weinberg equilibrium for the adult population for all the studied polymorphisms. Four SNPs in CYP2R1 (rs1562902, rs7116978, rs10741657 and rs10766197) and six SNPs in GC (rs4588, rs842999, rs2282679, rs12512631, rs16846876 and rs17467825) were statistically significantly associated with serum 25(OH)D concentrations in children, adults and all combined.
Several of the SNPs were in strong linkage disequilibrium, and the associations were driven by CYP2R1-rs10741657 and rs10766197, and by GC-rs4588 and 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 risk alleles.
To conclude, our results provide supporting evidence that common polymorphisms in GC and CYP2R1 are associated with serum 25(OH)D concentrations in the Caucasian population and that certain haplotypes may predispose to lower 25(OH)D concentrations in late summer in Denmark.
Language: | English |
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Publisher: | Public Library of Science |
Year: | 2014 |
Pages: | e89907 |
ISSN: | 19326203 |
Types: | Journal article |
DOI: | 10.1371/journal.pone.0089907 |
ORCIDs: | Nissen, Ioanna , Ravn-Haren, Gitte , Andersen, Rikke and Mejborn, Heddie |
Adolescent Adult Alleles CYP2R1 protein, human Child Child, Preschool Cholestanetriol 26-Monooxygenase Cross-Sectional Studies Cytochrome P450 Family 2 Denmark Female Genetic Association Studies Genetic Variation Haplotypes Healthy Volunteers Humans Male Medicine Middle Aged Polymorphism, Single Nucleotide Q R Risk Factors Science Vitamin D Vitamin D-Binding Protein Young Adult