Funded in part by Amgen, Eli Lilly and Company, Pfizer, Danone, Bupa Foundation, Servier, Nestec
Response to Antenatal Cholecalciferol Supplementation Is Associated With Common Vitamin D-Related Genetic Variants
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, Maternal Vitamin D Osteoporosis Study Trial Group
The Journal of clinical endocrinology and metabolism · 46 citations
Review labels
Neutral facts our review recorded about how this study was done. They describe method, never whether we like the result.
How it was studied
- Design
- Randomized controlled trial (indexed by PubMed)
- Studied in
- People
- Main outcome
- Health markers and function
Who paid for it
- Funding
- Industry funded
- Company
- Amgen
- Company
- Eli Lilly and Company
- Company
- Pfizer
- Company
- Danone
- Nonprofit
- Wellcome Trust
- University or hospital
- University Hospital Southampton NHS Foundation Trust
- Government
- National Institute for Health and Care Research
- Company
- Bupa Foundation
- University or hospital
- University of Southampton
- University or hospital
- University of Oxford
- Government
- European Commission
- Company
- Servier
- Nonprofit
- Versus Arthritis
- Company
- Nestec
- University or hospital
- National Institute for Health Research Southampton Biomedical Research Centre
- Government
- Medical Research Council
- Government
- National Institute for Health Research (NIHR)
- Grants
- Medical Research Council (FP7/20072013); Wellcome Trust (FP7/2007–2013); National Institute for Health Research Southampton Biomedical Research Centre (289346); National Institute for Health and Care Research (10/33/04); European Commission (613977); Wellcome Trust (201222/Z/16/Z); National Institute for Health and Care Research (FP7/2007–2013); National Institute for Health and Care Research (HTA/10/33/04); European Commission (2007–2013); National Institute for Health Research Southampton Biomedical Research Centre (FP7/2007-2013); National Institute for Health and Care Research (ACF-2014-26-002); National Institute for Health and Care Research (NF-SI-0515-10042); Medical Research Council (MC_UU_12011/4); Versus Arthritis (21231); European Commission (FP7 2007-2013); Medical Research Council (U105960371); National Institute for Health and Care Research (613977); University of Oxford (U105960371); National Institute for Health and Care Research (NF-SI-0508-10082); National Institute for Health and Care Research (289346); European Commission (FP7/2007); Versus Arthritis (17702); Medical Research Council (MC_UU_12011/2); Medical Research Council (4050502589); Medical Research Council (MC_UU_12011/1); National Institute for Health and Care Research (NF-SI-0513-10085); Wellcome Trust (201268); European Commission (289346); Wellcome Trust (201268/Z/16/Z)
Based on 17 listed funder(s).
Publication
- Published
- 2017-05-29 · J Clin Endocrinol Metab · vol. 102 · issue 8 · pp. 2941–2949
- Publisher
- Oxford University Press
- Cited
- 59 citations · more than 96% of similar papers · 4.5× the field average
- Impact
- Top 10% most cited in its field
- References
- 33 works
- Access
- Open access (hybrid journal) · CC-BY
- Research areas
- Vitamin D Research Studies · Birth, Development, and Health · Per- and polyfluoroalkyl substances research
- Keywords
- Cholecalciferol, Vitamin D and neurology, CYP24A1, Internal medicine, Medicine, vitamin D deficiency, Endocrinology, Single-nucleotide polymorphism, Gestational age, Vitamin, Vitamin D-binding protein, Calcitriol receptor, Pregnancy, Biology, Genetics, Genotype
- MeSH
- humans, vitamin d deficiency, cholecalciferol, oxidoreductases acting on ch-ch group donors, vitamins, vitamin d, vitamin d-binding protein, treatment outcome, multivariate analysis, linear models, double-blind method, pregnancy, genotype, polymorphism, single nucleotide, alleles, dietary supplements, adult, female, young adult, cholestanetriol 26-monooxygenase, vitamin d3 24-hydroxylase, cytochrome p450 family 2
21 authors
From GB
- Rebecca Jane MoonNational Health Service; University Hospital Southampton NHS Foundation Trust; MRC Lifecourse Epidemiology Unit; University of Southampton; Medical Research Council
- Nicholas C. HarveyNational Health Service; University Hospital Southampton NHS Foundation Trust; National Institute for Health and Care Research; MRC Lifecourse Epidemiology Unit; University of Southampton; Medical Research Council
- Cyrus CooperNational Health Service; University Hospital Southampton NHS Foundation Trust; National Institute for Health and Care Research; University of Oxford; NIHR Oxford Biomedical Research Centre; MRC Lifecourse Epidemiology Unit; University of Southampton; Medical Research Council
- Stefania D’AngeloMRC Lifecourse Epidemiology Unit; University of Southampton; Medical Research Council
- Elizabeth Mary CurtisMRC Lifecourse Epidemiology Unit; University of Southampton; Medical Research Council
- Sarah CrozierMRC Lifecourse Epidemiology Unit; University of Southampton; Medical Research Council
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.
Abstract via Europe PMC. Copyright remains with the authors or publisher (CC BY).
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