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Randomized Controlled Trial
. 2017 Aug 1;102(8):2941-2949.
doi: 10.1210/jc.2017-00682.

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

Rebecca J Moon  1   2 , Nicholas C Harvey  1   3 , Cyrus Cooper  1   3   4 , Stefania D'Angelo  1 , Elizabeth M Curtis  1 , Sarah R Crozier  1 , Sheila J Barton  1 , Sian M Robinson  1   3 , Keith M Godfrey  1   3 , Nikki J Graham  5 , John W Holloway  5 , Nicholas J Bishop  6 , Stephen Kennedy  7 , Aris T Papageorghiou  7 , Inez Schoenmakers  8   9 , Robert Fraser  10 , Saurabh V Gandhi  10 , Ann Prentice  8 , Hazel M Inskip  1   3 , M Kassim Javaid  4 ; Maternal Vitamin D Osteoporosis Study Trial Group
Affiliations
Randomized Controlled Trial

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

Rebecca J Moon et al. J Clin Endocrinol Metab. .

Abstract

Context: Single-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.

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 Maternal Vitamin D Osteoporosis Study trial of antenatal cholecalciferol supplementation.

Setting: Hospital antenatal clinics.

Participants: In 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.

Interventions: 1000 IU/d cholecalciferol from 14 weeks of gestation until delivery.

Main outcome measure: 25(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].

Results: Only 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.

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.

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Figures

Figure 1.
Figure 1.
Consolidated Standards of Reporting Trials diagram.
Figure 2.
Figure 2.
25(OH)D before and after supplementation with cholecalciferol in pregnancy according to GRS for the SNPs rs10741657 (CYP2R1) and rs2282679 (GC). Shown as mean and 95% CI for each group. P is for trend by linear regression with adjustment for confounders.
Figure 3.
Figure 3.
Associations between SNPs and change in 25(OH)D from 14 to 34 weeks of gestation following supplementation with 1000 IU/d cholecalciferol. Shown as β and 95% CI. The homozygous low-frequency allele was used as the reference group, with the β representing the change in 25(OH)D (nmol/L) per common allele (additive model). Models were adjusted for age, physical activity, smoking status, educational attainment, season of blood sampling, compliance, and pregnancy weight gain.
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Comment in

References

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