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Response to antenatal Cholecalciferol supplementation is associated with common vitamin D–Related Genetic Variants

Response to antenatal Cholecalciferol supplementation is associated with common vitamin D–Related Genetic Variants
Response to antenatal Cholecalciferol supplementation is associated with common vitamin D–Related Genetic Variants
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 = 25.2 nmol/L; 95% CI, 28.2 to 22.2 nmol/L; P = 0.001) and rs2282679 (GC) (β = 4.2 nmol/L; 95% CI, 0.9 to 7.5 nmol/L; Ρ = 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.
0021-972X
2941-2949
Moon, Rebecca J.
954fb3ed-9934-4649-886d-f65944985a6b
Harvey, Nicholas C.
ce487fb4-d360-4aac-9d17-9466d6cba145
Cooper, Cyrus
e05f5612-b493-4273-9b71-9e0ce32bdad6
D'angelo, Stefania
13375ecd-1117-4b6e-99c0-32239f52eed6
Curtis, Elizabeth M.
12aba0c3-1e9e-49ef-a7e9-3247e649cdd6
Crozier, Sarah R.
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Barton, Sheila J.
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Robinson, Sian M.
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Godfrey, Keith M.
0931701e-fe2c-44b5-8f0d-ec5c7477a6fd
Graham, Nikki J.
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Holloway, John W.
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Bishop, Nicholas J.
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Kennedy, Stephen
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Papageorghiou, Aris T.
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Schoenmakers, Inez
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Fraser, Robert
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Gandhi, Saurabh V.
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Prentice, Ann
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Inskip, Hazel M.
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Javaid, M. Kassim
64155236-2ef0-4065-b684-cf723a888117
the MAVIDOS Trial Group
Moon, Rebecca J.
954fb3ed-9934-4649-886d-f65944985a6b
Harvey, Nicholas C.
ce487fb4-d360-4aac-9d17-9466d6cba145
Cooper, Cyrus
e05f5612-b493-4273-9b71-9e0ce32bdad6
D'angelo, Stefania
13375ecd-1117-4b6e-99c0-32239f52eed6
Curtis, Elizabeth M.
12aba0c3-1e9e-49ef-a7e9-3247e649cdd6
Crozier, Sarah R.
9c3595ce-45b0-44fa-8c4c-4c555e628a03
Barton, Sheila J.
4f674382-ca0b-44ad-9670-e71a0b134ef0
Robinson, Sian M.
ba591c98-4380-456a-be8a-c452f992b69b
Godfrey, Keith M.
0931701e-fe2c-44b5-8f0d-ec5c7477a6fd
Graham, Nikki J.
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Holloway, John W.
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Bishop, Nicholas J.
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Kennedy, Stephen
90c7a08c-188c-4986-80a9-202b9b3dbb1f
Papageorghiou, Aris T.
48974657-d399-4f7f-8b8b-5b9174b8fefa
Schoenmakers, Inez
b25daaac-b388-467c-a514-3a6f5029bc2e
Fraser, Robert
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Gandhi, Saurabh V.
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Prentice, Ann
675810ad-8022-453c-b3a3-8afff0e1a920
Inskip, Hazel M.
5fb4470a-9379-49b2-a533-9da8e61058b7
Javaid, M. Kassim
64155236-2ef0-4065-b684-cf723a888117

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 , the MAVIDOS 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. (doi:10.1210/jc.2017-00682).

Record type: Article

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 = 25.2 nmol/L; 95% CI, 28.2 to 22.2 nmol/L; P = 0.001) and rs2282679 (GC) (β = 4.2 nmol/L; 95% CI, 0.9 to 7.5 nmol/L; Ρ = 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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SNPs MAVIDOS JCEM 16_05_2017 R2 - Accepted Manuscript
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Accepted/In Press date: 24 May 2017
e-pub ahead of print date: 29 May 2017
Published date: 1 August 2017

Identifiers

Local EPrints ID: 412373
URI: http://eprints.soton.ac.uk/id/eprint/412373
ISSN: 0021-972X
PURE UUID: fb025c7b-8e87-4a05-80d8-90ee74c0fde1
ORCID for Nicholas C. Harvey: ORCID iD orcid.org/0000-0002-8194-2512
ORCID for Cyrus Cooper: ORCID iD orcid.org/0000-0003-3510-0709
ORCID for Stefania D'angelo: ORCID iD orcid.org/0000-0002-7267-1837
ORCID for Elizabeth M. Curtis: ORCID iD orcid.org/0000-0002-5147-0550
ORCID for Sarah R. Crozier: ORCID iD orcid.org/0000-0002-9524-1127
ORCID for Sheila J. Barton: ORCID iD orcid.org/0000-0003-4963-4242
ORCID for Sian M. Robinson: ORCID iD orcid.org/0000-0003-1766-7269
ORCID for Keith M. Godfrey: ORCID iD orcid.org/0000-0002-4643-0618
ORCID for John W. Holloway: ORCID iD orcid.org/0000-0001-9998-0464
ORCID for Hazel M. Inskip: ORCID iD orcid.org/0000-0001-8897-1749

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Date deposited: 17 Jul 2017 13:33
Last modified: 18 Feb 2021 17:30

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Contributors

Author: Rebecca J. Moon
Author: Cyrus Cooper ORCID iD
Author: Stefania D'angelo ORCID iD
Author: Sian M. Robinson ORCID iD
Author: Nikki J. Graham
Author: Nicholas J. Bishop
Author: Stephen Kennedy
Author: Aris T. Papageorghiou
Author: Inez Schoenmakers
Author: Robert Fraser
Author: Saurabh V. Gandhi
Author: Ann Prentice
Author: Hazel M. Inskip ORCID iD
Author: M. Kassim Javaid
Corporate Author: the MAVIDOS Trial Group

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