title: Common variants in CYP2R1 and GC genes predict vitamin D concentrations in healthy Danish children and adults.
abstract: 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.
authors.affiliation: Division of Nutrition, National Food Institute, Technical University of Denmark, Søborg, Denmark.
authors.forename: Janna
authors.initials: J
authors.lastname: Nissen
authors.affiliation: Division of Nutrition, National Food Institute, Technical University of Denmark, Søborg, Denmark.
authors.forename: Lone Banke
authors.initials: LB
authors.lastname: Rasmussen
authors.affiliation: Division of Toxicology and Risk Assessment, National Food Institute, Technical University of Denmark, Søborg, Denmark.
authors.forename: Gitte
authors.initials: G
authors.lastname: Ravn-Haren
authors.affiliation: Department of Applied Mathematics and Computer Science, Technical University of Denmark, Lyngby, Denmark.
authors.forename: Elisabeth Wreford
authors.initials: EW
authors.lastname: Andersen
authors.affiliation: Department of Biomedicine, Aarhus University, Aarhus, Denmark.
authors.forename: Bettina
authors.initials: B
authors.lastname: Hansen
authors.affiliation: Division of Nutrition, National Food Institute, Technical University of Denmark, Søborg, Denmark.
authors.forename: Rikke
authors.initials: R
authors.lastname: Andersen
authors.affiliation: Division of Nutrition, National Food Institute, Technical University of Denmark, Søborg, Denmark.
authors.forename: Heddie
authors.initials: H
authors.lastname: Mejborn
authors.affiliation: Division of Nutrition, National Food Institute, Technical University of Denmark, Søborg, Denmark.
authors.forename: Katja Howarth
authors.initials: KH
authors.lastname: Madsen
authors.affiliation: National Research Centre for the Working Environment, Copenhagen, Denmark.
authors.forename: Ulla
authors.initials: U
authors.lastname: Vogel
mesh_terms: D000293:Adolescent; D000328:Adult; D000483:Alleles; D002648:Child; D002675:Child, Preschool; D053493:Cholestanetriol 26-Monooxygenase / Q000235:genetics*; D003430:Cross-Sectional Studies; D000072467:Cytochrome P450 Family 2; D003718:Denmark; D005260:Female; D056726:Genetic Association Studies; D014644:Genetic Variation; D006239:Haplotypes; D064368:Healthy Volunteers; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D014807:Vitamin D / Q000097:blood*; D014809:Vitamin D-Binding Protein / Q000235:genetics*; D055815:Young Adult
chemical_list: D014809:Vitamin D-Binding Protein; D014807:Vitamin D; D000072467:Cytochrome P450 Family 2; C506833:CYP2R1 protein, human; D053493:Cholestanetriol 26-Monooxygenase