title: Common genetic variants are associated with lower serum 25-hydroxyvitamin D concentrations across the year among children at northern latitudes.
abstract: In a longitudinal study including 642 healthy 8-11-year-old Danish children, we investigated associations between vitamin D dependent SNP and serum 25-hydroxyvitamin D (25(OH)D) concentrations across a school year (August-June). Serum 25(OH)D was measured three times for every child, which approximated measurements in three seasons (autumn, winter, spring). Dietary and supplement intake, physical activity, BMI and parathyroid hormone were likewise measured at each time point. In all, eleven SNP in four vitamin D-related genes: Cytochrome P450 subfamily IIR1 (CYP2R1); 7-dehydrocholesterol reductase/nicotinamide adenine dinucleotide synthetase-1(DHCR7/NADSYN1); group-specific complement (GC); and vitamin D receptor were genotyped. We found minor alleles of CYP2R1 rs10500804, and of GC rs4588 and rs7041 to be associated with lower serum 25(OH)D concentrations across the three seasons (all P<0·01), with estimated 25(OH)D differences of -5·8 to -10·6 nmol/l from major to minor alleles homozygosity. In contrast, minor alleles homozygosity of rs10741657 and rs1562902 in CYP2R1 was associated with higher serum 25(OH)D concentrations compared with major alleles homozygosity (all P<0·001). Interestingly, the association between season and serum 25(OH)D concentrations was modified by GC rs7041 (P interaction=0·044), observed as absence of increase in serum 25(OH)D from winter to spring among children with minor alleles homozygous genotypes compared with the two other genotypes of rs7041 (P<0·001). Our results suggest that common genetic variants are associated with lower serum 25(OH)D concentrations across a school year. Potentially due to modified serum 25(OH)D response to UVB sunlight exposure. Further confirmation and paediatric studies investigating vitamin D-related health outcomes of these genotypic differences are needed.
authors.affiliation: 1University College Lillebaelt,Denmark,Niels Bohrs Allé 1,DK-5230 Odense M,Denmark.
authors.forename: Rikke A
authors.initials: RA
authors.lastname: Petersen
authors.affiliation: 2Department of Nutrition, Exercise and Sports, Faculty of Science,University of Copenhagen,Rolighedsvej 26,DK-1958 Frederiksberg C,Denmark.
authors.forename: Lesli H
authors.initials: LH
authors.lastname: Larsen
authors.affiliation: 2Department of Nutrition, Exercise and Sports, Faculty of Science,University of Copenhagen,Rolighedsvej 26,DK-1958 Frederiksberg C,Denmark.
authors.forename: Camilla T
authors.initials: CT
authors.lastname: Damsgaard
authors.affiliation: 2Department of Nutrition, Exercise and Sports, Faculty of Science,University of Copenhagen,Rolighedsvej 26,DK-1958 Frederiksberg C,Denmark.
authors.forename: Louise B
authors.initials: LB
authors.lastname: Sørensen
authors.affiliation: 2Department of Nutrition, Exercise and Sports, Faculty of Science,University of Copenhagen,Rolighedsvej 26,DK-1958 Frederiksberg C,Denmark.
authors.forename: Mads F
authors.initials: MF
authors.lastname: Hjorth
authors.affiliation: 3Risk benefit Research Group,The National Food Institute,Technical University of Denmark,Mørkhøj Bygade 19,DK-2860 Søborg,Denmark.
authors.forename: Rikke
authors.initials: R
authors.lastname: Andersen
authors.affiliation: 3Risk benefit Research Group,The National Food Institute,Technical University of Denmark,Mørkhøj Bygade 19,DK-2860 Søborg,Denmark.
authors.forename: Inge
authors.initials: I
authors.lastname: Tetens
authors.affiliation: 4Section of Molecular Diagnostics, Clinical Biochemistry,Aalborg University Hospital,Reberbansgade 15,DK-9000 Aalborg,Denmark.
authors.forename: Henrik
authors.initials: H
authors.lastname: Krarup
authors.affiliation: 2Department of Nutrition, Exercise and Sports, Faculty of Science,University of Copenhagen,Rolighedsvej 26,DK-1958 Frederiksberg C,Denmark.
authors.forename: Christian
authors.initials: C
authors.lastname: Ritz
authors.affiliation: 2Department of Nutrition, Exercise and Sports, Faculty of Science,University of Copenhagen,Rolighedsvej 26,DK-1958 Frederiksberg C,Denmark.
authors.forename: Arne
authors.identifier: http://orcid.org/0000-0001-8968-8996
authors.initials: A
authors.lastname: Astrup
authors.affiliation: 2Department of Nutrition, Exercise and Sports, Faculty of Science,University of Copenhagen,Rolighedsvej 26,DK-1958 Frederiksberg C,Denmark.
authors.forename: Kim F
authors.initials: KF
authors.lastname: Michaelsen
authors.affiliation: 2Department of Nutrition, Exercise and Sports, Faculty of Science,University of Copenhagen,Rolighedsvej 26,DK-1958 Frederiksberg C,Denmark.
authors.forename: Christian
authors.initials: C
authors.lastname: Mølgaard
mesh_terms: D000483:Alleles; D002648:Child; D053493:Cholestanetriol 26-Monooxygenase / Q000235:genetics; D000072467:Cytochrome P450 Family 2 / Q000235:genetics; D003718:Denmark; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D044925:Oxidoreductases Acting on CH-CH Group Donors / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D018167:Receptors, Calcitriol / Q000235:genetics; D012574:Schools; D012621:Seasons; D014466:Ultraviolet Rays; D014807:Vitamin D / Q000031:analogs & derivatives* / Q000097:blood; D014808:Vitamin D Deficiency / Q000097:blood / Q000235:genetics*; D014809:Vitamin D-Binding Protein / Q000235:genetics
chemical_list: D018167:Receptors, Calcitriol; C579457:VDR protein, human; D014809:Vitamin D-Binding Protein; D014807:Vitamin D; C104450:25-hydroxyvitamin D; D000072467:Cytochrome P450 Family 2; C506833:CYP2R1 protein, human; D053493:Cholestanetriol 26-Monooxygenase; D044925:Oxidoreductases Acting on CH-CH Group Donors; C019995:7-dehydrocholesterol reductase
keywords:  
                    CYP2R1
                  cytochrome P450 subfamily IIR1;  
                    GC
                  group-specific complement;  25(OH)D 25-hydroxyvitamin D;  DBP vitamin D-binding protein;  PTH parathyroid hormone; Children; Genetic variations; Northern latitudes; Vitamin D