Response to 1000 IU of vitamin D varies by about 4 percent due to gene variants – RCT July 2014

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.

J Clin Endocrinol Metab. 2014 Jul 29:jc20141389. [Epub ahead of print]
Barry EL1, Rees JR, Peacock JL, Mott LA, Amos CI, Bostick RM, Figueiredo JC, Ahnen DJ, Bresalier RS, Burke CA, Baron JA.
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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.

PMID: 25070320
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Comment by VitaminDWiki

• Genes (1.04 X) appear to play a small part in the 2X variations in vitamin D response between individuals
• This study does not look at the much large reduction of Vitamin D getting to cells due to the Vitamin D receptor gene

See also VitaminDWiki

• Genetics category listing and associated searches for many of the genes mentioned in this study
• All items in category Vitamin D Receptor 530 items
• All items in category Vitamin D Binding Protein 178 items
• Common Vitamin D gene variants and resulting diseases – Jan 2013
• 291 genes improved expression by 2000 IU of vitamin D – RCT March 2013
• How you might double your response to vitamin D
• Overview Vitamin D Dose-Response has graphs showing the huge response differences between individuals - a small portion of which is due to gene variants