Petersen Rikke A, Larsen Lesli H, Damsgaard Camilla T, Sørensen Louise B, Hjorth Mads F, Andersen Rikke, Tetens Inge, Krarup Henrik, Ritz Christian, Astrup Arne, Michaelsen Kim F, Mølgaard Christian
1University College Lillebaelt,Denmark,Niels Bohrs Allé 1,DK-5230 Odense M,Denmark.
2Department of Nutrition, Exercise and Sports, Faculty of Science,University of Copenhagen,Rolighedsvej 26,DK-1958 Frederiksberg C,Denmark.
Br J Nutr. 2017 Mar;117(6):829-838. doi: 10.1017/S0007114517000538. Epub 2017 Apr 6.
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.
在一项纳入642名8至11岁丹麦健康儿童的纵向研究中，我们调查了维生素D相关单核苷酸多态性（SNP）与一学年（8月至6月）血清25-羟基维生素D（25(OH)D）浓度之间的关联。对每个儿童的血清25(OH)D进行了三次测量，这大致相当于三个季节（秋季、冬季、春季）的测量值。在每个时间点同样测量了饮食和补充剂摄入量、身体活动、体重指数和甲状旁腺激素。总共对四个维生素D相关基因中的11个SNP进行了基因分型：细胞色素P450亚家族IIR1（CYP2R1）；7-脱氢胆固醇还原酶/烟酰胺腺嘌呤二核苷酸合成酶-1（DHCR7/NADSYN1）；群体特异性补体（GC）；以及维生素D受体。我们发现，CYP2R1 rs10500804、GC rs4588和rs7041的次要等位基因与三个季节中较低的血清25(OH)D浓度相关（所有P<0.01），从主要等位基因纯合子到次要等位基因纯合子，估计25(OH)D差异为-5.8至-10.6 nmol/l。相比之下，与主要等位基因纯合子相比，CYP2R1中rs10741657和rs1562902的次要等位基因纯合子与较高的血清25(OH)D浓度相关（所有P<0.001）。有趣的是，季节与血清25(OH)D浓度之间的关联被GC rs7041改变（P交互作用=0.044），观察到rs7041次要等位基因纯合基因型儿童与其他两种基因型相比，从冬季到春季血清25(OH)D没有增加（P<0.001）。我们的结果表明，常见的基因变异与一学年中较低的血清25(OH)D浓度相关。可能是由于血清25(OH)D对紫外线阳光照射的反应改变。需要进一步证实以及进行儿科研究来调查这些基因型差异与维生素D相关健康结果的关系。
