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Maternal and fetal genetic variation in vitamin D metabolism and umbilical cord blood 25-hydroxyvitamin D

Maternal and fetal genetic variation in vitamin D metabolism and umbilical cord blood 25-hydroxyvitamin D
Maternal and fetal genetic variation in vitamin D metabolism and umbilical cord blood 25-hydroxyvitamin D

Context: Single nucleotide polymorphisms (SNPs) in vitamin D metabolism pathway genes are associated with circulating 25-hydroxyvitamin D (25(OH)D) in adults. Less is known about the relationships between mother and offspring SNPs and umbilical cord blood 25(OH)D. Objective: (1) To undertake a meta-analysis of the relationships of maternal and offspring SNPs in the vitamin D metabolism pathway and cord blood 25(OH)D in pregnant women including novel data; and (2) to examine these relationships in women who received antenatal cholecalciferol supplementation in a clinical trial. Methods: Novel data analysis from an observational mother-offspring cohort study (Southampton Women's Survey) and the MAVIDOS double-blind, randomized, placebo-controlled trial of 1000 IU/day cholecalciferol supplementation in pregnancy, and an electronic literature search of published studies in PubMed up to 31 July 2021. Studies reporting associations between rs12785878 (DHCR7), rs10741657 (CYP2R1), rs6013897 (CYP24A1), or rs2282679 (GC) and cord blood 25(OH)D. One published study was included in addition to the novel data analysis. Associations between both maternal and offspring SNPs at rs2282679 (GC) and rs12785878 (DHCR7), and cord blood 25(OH)D were identified. When maternal genotype was adjusted for offspring genotype, and vice versa, there was persisting evidence for associations with maternal rs12785878 (β [95% CI] 1.6 nmol/L [0.3, 2.8] per common allele), and offspring rs2282679 (β 3.1 nmol/L ]2.0, 4.4] per common allele). Maternal and offspring SNPs at rs1074657 and rs613897 were not associated with cord blood 25(OH)D. Result: Associations between both maternal and offspring SNPs at rs2282679 (GC) and rs12785878 (DHCR7), and cord blood 25(OH)D were identified. When maternal genotype was adjusted for offspring genotype, and vice versa, there was persisting evidence for associations with maternal rs12785878 (β [95% CI] 1.6 nmol/L [0.3, 2.8] per common allele), and offspring rs2282679 (β 3.1 nmol/L ]2.0, 4.4] per common allele). Maternal and offspring SNPs at rs1074657 and rs613897 were not associated with cord blood 25(OH)D. Conclusion: Common genetic variation in the vitamin D metabolism pathway is associated with umbilical cord blood 25(OH)D.

25-hydroxyvitamin D, DHCR7, GC, single nucleotide polymorphism, umbilical cord blood, vitamin D
0021-972X
E3403-E3410
Moon, Rebecca
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Cooke, Laura, Diana Frances
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D'angelo, Stefania
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Curtis, Elizabeth
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Titcombe, Philip
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Davies, Justin
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Godfrey, Keith
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Cleal, Jane
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Lewis, Rohan
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Cooper, Cyrus
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Harvey, Nicholas
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Moon, Rebecca
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Cooke, Laura, Diana Frances
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D'angelo, Stefania
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Curtis, Elizabeth
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Titcombe, Philip
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Davies, Justin
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Godfrey, Keith
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Cleal, Jane
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Lewis, Rohan
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Cooper, Cyrus
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Harvey, Nicholas
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Moon, Rebecca, Cooke, Laura, Diana Frances, D'angelo, Stefania, Curtis, Elizabeth, Titcombe, Philip, Davies, Justin, Godfrey, Keith, Cleal, Jane, Lewis, Rohan, Cooper, Cyrus and Harvey, Nicholas (2022) Maternal and fetal genetic variation in vitamin D metabolism and umbilical cord blood 25-hydroxyvitamin D. Journal of Clinical Endocrinology & Metabolism, 107 (8), E3403-E3410. (doi:10.1210/clinem/dgac263).

Record type: Article

Abstract

Context: Single nucleotide polymorphisms (SNPs) in vitamin D metabolism pathway genes are associated with circulating 25-hydroxyvitamin D (25(OH)D) in adults. Less is known about the relationships between mother and offspring SNPs and umbilical cord blood 25(OH)D. Objective: (1) To undertake a meta-analysis of the relationships of maternal and offspring SNPs in the vitamin D metabolism pathway and cord blood 25(OH)D in pregnant women including novel data; and (2) to examine these relationships in women who received antenatal cholecalciferol supplementation in a clinical trial. Methods: Novel data analysis from an observational mother-offspring cohort study (Southampton Women's Survey) and the MAVIDOS double-blind, randomized, placebo-controlled trial of 1000 IU/day cholecalciferol supplementation in pregnancy, and an electronic literature search of published studies in PubMed up to 31 July 2021. Studies reporting associations between rs12785878 (DHCR7), rs10741657 (CYP2R1), rs6013897 (CYP24A1), or rs2282679 (GC) and cord blood 25(OH)D. One published study was included in addition to the novel data analysis. Associations between both maternal and offspring SNPs at rs2282679 (GC) and rs12785878 (DHCR7), and cord blood 25(OH)D were identified. When maternal genotype was adjusted for offspring genotype, and vice versa, there was persisting evidence for associations with maternal rs12785878 (β [95% CI] 1.6 nmol/L [0.3, 2.8] per common allele), and offspring rs2282679 (β 3.1 nmol/L ]2.0, 4.4] per common allele). Maternal and offspring SNPs at rs1074657 and rs613897 were not associated with cord blood 25(OH)D. Result: Associations between both maternal and offspring SNPs at rs2282679 (GC) and rs12785878 (DHCR7), and cord blood 25(OH)D were identified. When maternal genotype was adjusted for offspring genotype, and vice versa, there was persisting evidence for associations with maternal rs12785878 (β [95% CI] 1.6 nmol/L [0.3, 2.8] per common allele), and offspring rs2282679 (β 3.1 nmol/L ]2.0, 4.4] per common allele). Maternal and offspring SNPs at rs1074657 and rs613897 were not associated with cord blood 25(OH)D. Conclusion: Common genetic variation in the vitamin D metabolism pathway is associated with umbilical cord blood 25(OH)D.

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Accepted/In Press date: 22 April 2022
e-pub ahead of print date: 26 April 2022
Published date: 1 August 2022
Additional Information: Funding Information: This work was supported by grants from the Arthritis Research UK (17702), Medical Research Council (MC_PC_21003; MC_PC_21001), Bupa Foundation, National Institute for Health Research (NIHR) Southampton Biomedical Research Centre, University of Southampton and University Hospital Southampton NHS Foundation Trust, and NIHR Musculoskeletal Biomedical Research Unit, University of Oxford. The work leading to these results was supported by the European Union’s Seventh Framework Programme (FP7/2007-2013), projects EarlyNutrition and ODIN under grant agreements numbers 289346 and 613977. K.M.G. is supported by the National Institute for Health Research (NIHR Senior Investigator (NF-SI-0515-10042) and NIHR Southampton 1000DaysPlus Global Nutrition Research Group (17/63/154)), the European Union (Erasmus + Programme ImpENSA 598488-EPP-1-2018-1-DE-EPPKA2-CBHE-JP) and the British Heart Foundation (RG/15/17/3174, SP/F/21/150013). R.J.M. and E.M.C. are funded by NIHR Academic Clinical Lectureships. L.D.F.C. is supported by the Gerald Kerkut Charitable Trust. We are extremely grateful to Merck GmbH for the kind provision of the Vigantoletten supplement in the MAVIDOS trial. Merck GmbH had no role in the trial execution, data collection, analysis, or manuscript preparation. Funding Information: R.J.M., L.D.F.C., S.D., J.C., and R.L. have nothing to disclose. C.C. reports personal fees from ABBH, Amgen, Eli Lilly, GSK, Medtronic, Merck, Novartis, Pfizer, Roche, Servier, and Takeda, outside the submitted work. N.C.H. reports personal fees, consultancy, lecture fees, and honoraria from Alliance for Better Bone Health, AMGEN, MSD, Eli Lilly, Servier, Shire, Consilient Healthcare, and Internis Pharma, outside the submitted work. K.M.G. reports reimbursement for speaking at Nestle Nutrition Institute conferences, grants from Abbott Nutrition and Nestec, outside the submitted work; in addition, K.M.G. has a patent Phenotype Prediction pending, a patent Predictive Use of CpG Methylation pending, and a patent Maternal Nutrition Composition pending, not directly related to this work. P.T. is part of academic research programs that have received research funding from Abbott Nutrition, Nestec, and Danone, outside the submitted work. J.H.D. has received travel bursaries from Novo Nordisk, SANDOZ, and Pfizer unrelated to this work. E.M.C. reports lecture fees and travel support from Eli Lilly, Pfizer, and UCB, outside the submitted work. Publisher Copyright: © 2022 Endocrine Society. All rights reserved.
Keywords: 25-hydroxyvitamin D, DHCR7, GC, single nucleotide polymorphism, umbilical cord blood, vitamin D

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Local EPrints ID: 457055
URI: http://eprints.soton.ac.uk/id/eprint/457055
ISSN: 0021-972X
PURE UUID: 19612e4d-1c46-4434-8d72-a094c57de7dd
ORCID for Laura, Diana Frances Cooke: ORCID iD orcid.org/0000-0002-8099-9437
ORCID for Stefania D'angelo: ORCID iD orcid.org/0000-0002-7267-1837
ORCID for Elizabeth Curtis: ORCID iD orcid.org/0000-0002-5147-0550
ORCID for Philip Titcombe: ORCID iD orcid.org/0000-0002-7797-8571
ORCID for Keith Godfrey: ORCID iD orcid.org/0000-0002-4643-0618
ORCID for Jane Cleal: ORCID iD orcid.org/0000-0001-7978-4327
ORCID for Rohan Lewis: ORCID iD orcid.org/0000-0003-4044-9104
ORCID for Cyrus Cooper: ORCID iD orcid.org/0000-0003-3510-0709
ORCID for Nicholas Harvey: ORCID iD orcid.org/0000-0002-8194-2512

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Date deposited: 20 May 2022 16:49
Last modified: 08 Oct 2022 02:00

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Contributors

Author: Rebecca Moon
Author: Laura, Diana Frances Cooke ORCID iD
Author: Stefania D'angelo ORCID iD
Author: Philip Titcombe ORCID iD
Author: Justin Davies
Author: Keith Godfrey ORCID iD
Author: Jane Cleal ORCID iD
Author: Rohan Lewis ORCID iD
Author: Cyrus Cooper ORCID iD
Author: Nicholas Harvey ORCID iD

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