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Financiado en parte por 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 citas

Etiquetas de revisión

Financiado por la industria

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Cómo se estudió

Diseño
Ensayo controlado aleatorizado (indexado por PubMed)
Estudiado en
Personas
Resultado principal
Marcadores de salud y funcionamiento

Quién lo pagó

Financiación
Financiado por la industria
Empresa
Amgen
Empresa
Eli Lilly and Company
Empresa
Pfizer
Empresa
Danone
Organización sin fines de lucro
Wellcome Trust
Universidad u hospital
University Hospital Southampton NHS Foundation Trust
Gobierno
National Institute for Health and Care Research
Empresa
Bupa Foundation
Universidad u hospital
University of Southampton
Universidad u hospital
University of Oxford
Gobierno
European Commission
Empresa
Servier
Organización sin fines de lucro
Versus Arthritis
Empresa
Nestec
Universidad u hospital
National Institute for Health Research Southampton Biomedical Research Centre
Gobierno
Medical Research Council
Gobierno
National Institute for Health Research (NIHR)
Subvenciones
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)

Según 17 financiadores declarados.

Publicación

Publicado
2017-05-29 · J Clin Endocrinol Metab · vol. 102 · número 8 · págs. 2941–2949
Editorial
Oxford University Press
Citado
59 citas · más que el 96% de estudios similares · 4.5× el promedio de su campo
Impacto
Entre el 10 % más citado de su campo
Referencias
33 trabajos
Acceso
Acceso abierto (revista híbrida) · CC-BY
Áreas de investigación
Vitamin D Research Studies · Birth, Development, and Health · Per- and polyfluoroalkyl substances research
Palabras clave
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 autores

  • Rebecca Jane Moon🇬🇧National Health Service; University Hospital Southampton NHS Foundation Trust; MRC Lifecourse Epidemiology Unit; University of Southampton; Medical Research Council
  • Nicholas C. Harvey🇬🇧National 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 Cooper🇬🇧National 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’Angelo🇬🇧MRC Lifecourse Epidemiology Unit; University of Southampton; Medical Research Council
  • Elizabeth Mary Curtis🇬🇧MRC Lifecourse Epidemiology Unit; University of Southampton; Medical Research Council
  • Sarah Crozier🇬🇧MRC Lifecourse Epidemiology Unit; University of Southampton; Medical Research Council
  • Sheila J. Barton🇬🇧MRC Lifecourse Epidemiology Unit; University of Southampton; Medical Research Council
  • Sian M. Robinson🇬🇧National 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
  • Keith M. Godfrey🇬🇧National 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
  • Nikki J. Graham🇬🇧University of Southampton
  • John W. Holloway🇬🇧University of Southampton
  • Nicholas J. Bishop🇬🇧Sheffield Children's Hospital; University of Sheffield
  • Stephen Kennedy🇬🇧John Radcliffe Hospital; University of Oxford
  • Aris T. Papageorghiou🇬🇧John Radcliffe Hospital; University of Oxford
  • Inez Schoenmakers🇬🇧University of East Anglia; MRC Elsie Widdowson Laboratory; Medical Research Council
  • Robert Fraser🇬🇧National Health Service; University of Sheffield
  • Saurabh V. Gandhi🇬🇧National Health Service; University of Sheffield
  • Ann Prentice🇬🇧MRC Elsie Widdowson Laboratory; Medical Research Council
  • Hazel M. Inskip🇬🇧National 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
  • M K Javaid🇬🇧National Institute for Health and Care Research; University of Oxford; NIHR Oxford Biomedical Research Centre
  • the Maternal Vitamin D Osteoporosis Study Trial Group

Resumen

El texto original del estudio, en el idioma en que se publicó.

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.

Resumen vía Europe PMC. Los derechos de autor siguen siendo de los autores o la editorial (CC BY).

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