Moon, Rebecca J., Harvey, Nicholas C., Cooper, Cyrus, D'angelo, Stefania, Curtis, Elizabeth M., Crozier, Sarah R., Barton, Sheila J., Robinson, Sian M., Godfrey, Keith M., Graham, Nikki J., Holloway, John W., Bishop, Nicholas J., Kennedy, Stephen, Papageorghiou, Aris T., Schoenmakers, Inez, Fraser, Robert, Gandhi, Saurabh V., Prentice, Ann, Inskip, Hazel M. and Javaid, M. Kassim , (2017) Response to antenatal Cholecalciferol supplementation is associated with common vitamin D–Related Genetic Variants. Journal of Clinical Endocrinology & Metabolism, 102 (8), 2941-2949. (doi:10.1210/jc.2017-00682).
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 =
25.2 nmol/L; 95% CI, 28.2 to 22.2 nmol/L; P = 0.001) and rs2282679 (GC) (β = 4.2 nmol/L; 95% CI, 0.9
to 7.5 nmol/L; Ρ = 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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