Response to antenatal cholecalciferol supplementation is associated with common vitamin D related genetic variants.

Response to antenatal cholecalciferol supplementation is associated with common vitamin D related genetic variants.

J Clin Endocrinol Metab. 2017 May 29;:

Authors: Moon RJ, Harvey NC, Cooper C, D'Angelo S, Curtis EM, Crozier SR, Barton SJ, Robinson SM, Godfrey KM, Graham NJ, Holloway JW, Bishop NJ, Kennedy S, Papageorghiou AT, Schoenmakers I, Fraser R, Gandhi SV, Prentice A, Inskip HM, Javaid MK, MAVIDOS Trial Group

Abstract
Context: Single nucleotide polymorphisms (SNP) 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.
Objective: To determine whether SNPs in DHCR7, CYP2R1, CYP24A1 and GC are associated with the response to gestational cholecalciferol supplementation.
Design: Within-randomization-group analysis of the MAVIDOS trial of antenatal cholecalciferol supplementation.
Setting: Hospital antenatal clinics.
Participants: 682 women of White ethnicity (351 placebo, 331 cholecalciferol) were included. SNPs at rs12785878 (DHCR7), rs10741657 (CYP2R1), rs6013897 (CYP24A1) and rs2282679 (GC) were genotyped.
Interventions: 1000 IU/day cholecalciferol from 14 weeks gestation until delivery.
Main Outcome Measure: 25(OH)D at randomisation and 34 weeks gestation were measured in a single batch (Diasorin Liaison). Associations between 25(OH)D and the SNPs were assessed by linear regression using an additive model (beta represents the change in 25(OH)D per additional common allele).
Results: Only rs12785878 (DHCR7) was associated with baseline 25(OH)D [β=3.1nmol/l (95% CI 1.0, 5.2), p<0.004]. In contrast, rs10741657 (CYP2R1) [β=-5.2nmol/l (95%CI -8.2, -2.2), p=0.001] and rs2282679 (GC) [β=4.2nmol/l (95%CI 0.9, 7.5), p=0.01] were associated with achieved 25(OH)D status following supplementation, while rs12785878 and rs6013897 (CYP24A1) were not.
Conclusions: Genetic 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.

PMID: 28575224 [PubMed - as supplied by publisher]

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