Genetic Variants in CYP2R1, CYP24A1 and VDR Modify the Efficacy of Vitamin D3 Supplementation for Increasing Serum 25-Hydroxyvitamin D Levels in a Randomized Controlled Trial

Elizabeth L Barry, Judy R Rees, Janet L Peacock, Leila A Mott, Christopher I Amos, Roberd M Bostick, Jane C Figueiredo, Dennis J Ahnen, Robert S Bresalier, Carol A Burke, John A Baron

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125 Citations (Scopus)

Abstract

Context: Adequate serum 25-hydroxyvitamin D concentrations [25(OH)D] are required for optimal bone health, and low levels are associated with chronic diseases.

Objective: We investigated whether 41 candidate single nucleotide polymorphisms (SNPs) in vitamin D and calcium pathway genes (GC, DHCR7, CYP2R1, CYP27B1, CYP24A1, VDR, and CASR) are associated with [25(OH)D] or modify the increase in [25(OH)D] from vitamin D3 supplementation.

Design and setting: Baseline and year one [25(OH)D] measurements from a randomized controlled trial conducted at 11 clinical centers in the United States.

Participants: 1,787 healthy non-Hispanic white participants aged 45-75 years.

Interventions: Vitamin D3 (1000 IU/day), calcium carbonate (1200 mg/day elemental), both or placebo.

Main outcome measures: Genotype main effects and interactions with vitamin D3 treatment estimated using multiple linear regression.

Results: The mean baseline serum [25(OH)D] was 25.4 ± 8.7 ng/ml. Associations with baseline levels were discovered for SNPs in CYP24A1 (rs2209314, rs2762939) and confirmed for SNPs in GC and CYP2R1. After one year, [25(OH)D] increased on average by 6.1 ± 8.9 ng/ml on vitamin D3 treatment and decreased by 1.1 ± 8.4 ng/ml on placebo. The increase in [25(OH)D] due to vitamin D3 supplementation was modified by genotypes at rs10766197 near CYP2R1, rs6013897 near CYP24A1, and rs7968585 near VDR.

Conclusions: The increase in [25(OH)D] attributable to vitamin D3 supplementation may vary according to common genetic differences in vitamin D 25-hydroxylase (CYP2R1), 24-hydroxylase (CYP24A1), and the vitamin D receptor (VDR) genes. These findings have implications for achieving optimal vitamin D status and potentially for vitamin D-related health outcomes.
Original languageEnglish
Number of pages6
JournalThe Journal of clinical endocrinology and metabolism
Early online date29 Jul 2014
DOIs
Publication statusE-pub ahead of print - 29 Jul 2014

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