期刊
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
卷 102, 期 8, 页码 2941-2949出版社
OXFORD UNIV PRESS INC
DOI: 10.1210/jc.2017-00682
关键词
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资金
- Arthritis Research UK [17702]
- Medical Research Council [4050502589, U105960371]
- Bupa Foundation
- Wellcome Trust National Institute for Health Research Southampton Biomedical Research Centre, University of Southampton [201268/Z/16/Z]
- University Hospital Southampton NHS Foundation Trust
- National Institute for Health Research Musculoskeletal Biomedical Research Unit, University of Oxford
- European Union's Seventh Framework Programme
- projects EarlyNutrition and Food-Based Solutions for Optimal Vitamin D Nutrition and Health Through the Life Cycle [289346, 613977]
- Medical Research Council [MC_U147585824, MC_UU_12011/4, G0400491, MC_U147585819, MC_UP_A620_1015, MC_U147585827, MC_UP_A620_1014, U1475000002, MC_U105960371, U1475000001, MC_UU_12011/2, MC_UU_12011/1] Funding Source: researchfish
- National Institute for Health Research [10/33/04, NF-SI-0513-10085, NF-SI-0515-10042, ACF-2014-26-002, NF-SI-0508-10082] Funding Source: researchfish
- Versus Arthritis [17702, 21231] Funding Source: researchfish
- Wellcome Trust [201222/Z/16/Z] Funding Source: researchfish
- MRC [MC_U147585819, MC_U105960371, G0400491, MC_UU_12011/4, MC_UP_A620_1015, MC_UU_12011/2, MC_U147585827] Funding Source: UKRI
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 [beta represents the change in 25(OH)D per additional common allele]. Results: Only rs12785878 (DHCR7) was associated with baseline 25(OH) D [beta = 3.1 nmol/L; 95% confidence interval (CI), 1.0 to 5.2 nmol/L; P < 0.004]. In contrast, rs10741657 (CYP2R1) (beta = 25.2 nmol/L; 95% CI, -8.2 to -2.2 nmol/L; P = 0.001) and rs2282679 (GC) (beta = 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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