Dataset Information

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.

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 1 [25(OH)D] measurements from a randomized controlled trial conducted at 11 clinical centers in the United States.

Participants

A total of 1787 healthy non-Hispanic white participants aged 45-75 years.

Interventions

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

Main outcome measures

Genotype main effects and interactions with vitamin D3 treatment estimated using multiple linear regression.

Results

The baseline serum [25(OH)D] was 25.4 ± 8.7 ng/mL (mean ± SD). Associations with baseline levels were discovered for SNPs in CYP24A1 (rs2209314, rs2762939) and confirmed for SNPs in GC and CYP2R1. After 1 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.

SUBMITTER: Barry EL

PROVIDER: S-EPMC4184076 | biostudies-literature | 2014 Oct

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

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.

Barry Elizabeth L EL Rees Judy R JR Peacock Janet L JL Mott Leila A LA Amos Christopher I CI Bostick Roberd M RM Figueiredo Jane C JC Ahnen Dennis J DJ Bresalier Robert S RS Burke Carol A CA Baron John A JA

The Journal of clinical endocrinology and metabolism 20140729 10

<h4>Context</h4>Adequate serum 25-hydroxyvitamin D concentrations, [25(OH)D], are required for optimal bone health, and low levels are associated with chronic diseases.<h4>Objective</h4>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.<h4>Design and setting</h4>Baseline and year 1 [ ...[more]

PMID: 25070320

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Project description:Vitamin D signaling is important for intestinal homeostasis. An increase in vitamin D receptors in immune cells can modulate cell phenotype and cytokine secretion. Cytokines regulate both pro- (interleukin 17; IL-17) and anti-inflammatory (IL-10) responses triggered by external stimuli. Inflammation in intestinal tissues can disrupt the structure and the remodeling of epithelial tight junction complexes, thus, compromising the protective barrier. The objective of the study was to determine the impact of dietary supplementation with 25-hydroxycholecalciferol (25OHD3), a hydroxylated metabolite of vitamin D, on intestinal cytokine abundance and epithelial barrier integrity over time in broilers. A randomized complete block design experiment was conducted to evaluate the effect of dietary 25OHD3 inclusion on relative protein expression of the cytokines, IL-17 and IL-10, and tight junction proteins, Zona Occludens 1 (ZO-1), and Claudin-1 (CLD-1), in broiler chicken duodenum and ileum from 3 to 21 days post-hatch. On day 0, male chicks (n = 168) were randomly assigned to raised floor pens. Experimental corn-soybean meal-based treatments were as follows: (1) a common starter diet containing 5,000 IU of D3 per kg of feed (VITD3) and (2) a common starter diet containing 2,240 IU of D3 + 2,760 IU of 25OHD3 per kg of feed (25OHD3) fed from days 0 to 21. On days 3, 6, 9, 12, 15, 18, and 21, 12 birds per treatment were euthanized to collect tissue samples for quantitative, multiplex, and fluorescent Western blot analysis. Target proteins were quantified using Image Quant TL 8.1 and expressed relative to total protein. Feeding 25OHD3 post-hatch decreased ileal IL-10 (anti-inflammatory) protein expression in 21-day-old broilers compared with VITD3 only (P = 0.0190). Broilers fed only VITD3 post-hatch had greater IL-17 (pro-inflammatory) protein expression in the ileum at 18 and 21 days-of-age (P = 0.0412) than those that fed 25OHD3. Dietary inclusion of 25OHD3 lowered the abundance of key inflammatory cytokines in the ileum of young broilers.

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Dataset Information

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.

Context

Objective

Design and setting

Participants

Interventions

Main outcome measures

Results

Conclusions

Publications

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.

Similar Datasets

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