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

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 and Maternal Vitamin D Osteoporosis Study Trial Group (2017) Response to antenatal cholecalciferol supplementation is associated with common vitamin D–related genetic variants. Journal of Clinical Endocrinology & Metabolism, 102 (8). 2941–2949. ISSN 0021-972X

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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.

Item Type: Article
Faculty \ School: Faculty of Medicine and Health Sciences > Norwich Medical School
UEA Research Groups: Faculty of Medicine and Health Sciences > Research Groups > Musculoskeletal Medicine
Faculty of Medicine and Health Sciences > Research Groups > Nutrition and Preventive Medicine
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Depositing User: Pure Connector
Date Deposited: 19 Aug 2017 05:07
Last Modified: 03 Nov 2022 15:43
DOI: 10.1210/jc.2017-00682


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