Journal Article

Response to Antenatal Cholecalciferol Supplementation Is Associated With Common Vitamin D–Related Genetic Variants

Curtis, Elizabeth M, Inskip, Hazel M, Gandhi, Saurabh V, Javaid, M Kassim, Papageorghiou, Aris T, Schoenmakers, Inez, Robinson, Sian M, D’Angelo, Stefania, Moon, Rebecca J, Graham, Nikki J, Bishop, Nicholas J, Fraser, Robert, Godfrey, Keith M, Holloway, John W, Cooper, Cyrus, Harvey, Nicholas C, Prentice, Ann, Barton, Sheila J, Crozier, Sarah R, Kennedy, Stephen

2017

Overview

ContextSingle-nucleotide polymorphisms (SNPs) in genes related to vitamin D metabolism have been associated with serum 25-hydroxyvitamin D [25(OH)D] concentration, but these relationships have not been examined following antenatal cholecalciferol supplementation.ObjectiveTo determine whether SNPs in DHCR7, CYP2R1, CYP24A1, and GC are associated with the response to gestational cholecalciferol supplementation.DesignWithin-randomization group analysis of the Maternal Vitamin D Osteoporosis Study trial of antenatal cholecalciferol supplementation.SettingHospital antenatal clinics.ParticipantsIn total, 682 women of white ethnicity (351 placebo, 331 cholecalciferol) were included. SNPs at rs12785878 (DHCR7), rs10741657 (CYP2R1), rs6013897 (CYP24A1), and rs2282679 (GC) were genotyped.Interventions1000 IU/d cholecalciferol from 14 weeks of gestation until delivery.Main Outcome Measure25(OH)D at randomization and 34 weeks of gestation were measured in a single batch (Liaison; Diasorin, Dartford, UK). Associations between 25(OH)D and the SNPs were assessed by linear regression using an additive model [β represents the change in 25(OH)D per additional common allele].ResultsOnly rs12785878 (DHCR7) was associated with baseline 25(OH)D [β = 3.1 nmol/L; 95% confidence interval (CI), 1.0 to 5.2 nmol/L; P < 0.004]. In contrast, rs10741657 (CYP2R1) (β = −5.2 nmol/L; 95% CI, −8.2 to −2.2 nmol/L; P = 0.001) and rs2282679 (GC) (β = 4.2 nmol/L; 95% CI, 0.9 to 7.5 nmol/L; P = 0.01) were associated with achieved 25(OH)D status following supplementation, whereas rs12785878 and rs6013897 (CYP24A1) were not.ConclusionsGenetic variation in DHCR7, which encodes 7-dehyrocholesterol reductase in the epidermal vitamin D biosynthesis pathway, appears to modify baseline 25(OH)D. In contrast, the response to antenatal cholecalciferol supplementation was associated with SNPs in CYP2R1, which may alter 25-hydroxylase activity, and GC, which may affect vitamin D binding protein synthesis or metabolite affinity.Associations between SNPs in the vitamin D metabolism pathway and 25(OH)D were assessed before and after antenatal vitamin D supplementation. The associations differed at the two time points.

• Publisher: Endocrine Society,Copyright Oxford University Press,Oxford University Press
• Subject: 25-Hydroxyvitamin D / 7-Dehydrocholesterol reductase / Adult / Alleles / Cholecalciferol - therapeutic use / Cholestanetriol 26-Monooxygenase - genetics / Clinical s / Cytochrome P450 Family 2 - genetics / Dietary Supplements / Double-Blind Method / Editor's Choice / Female / Genetic diversity / Genotype / Gestation / Humans / Hydroxylase / Linear Models / Metabolism / Metabolites / Minority & ethnic groups / Multivariate Analysis / Osteoporosis / Oxidoreductases Acting on CH-CH Group Donors - genetics / Polymorphism / Polymorphism, Single Nucleotide / Pregnancy / Protein biosynthesis / Single-nucleotide polymorphism / Supplements / Treatment Outcome / Vitamin D / Vitamin D - analogs & derivatives / Vitamin D - blood / Vitamin D Deficiency - prevention & control / Vitamin D-Binding Protein - genetics / Vitamin D3 24-Hydroxylase - genetics / Vitamins - therapeutic use / Young Adult