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CYP2R1 gene probably responsible for low vitamin D response – RCT April 2014

Environmental, personal and genetic determinants of response to vitamin D supplementation in older adults.

J Clin Endocrinol Metab. 2014 Apr 2:jc20134101. [Epub ahead of print]
Waterhouse M1, Tran B, Armstrong BK, Baxter C, Ebeling PR, English DR, Gebski V, Hill C, Kimlin MG, Lucas RM, Venn A, Webb PM, Whiteman DC, Neale RE.
1Population Health Division, QIMR Berghofer Medical Research Institute; Australia

Context and Objective: Suboptimal vitamin D status can be corrected by vitamin D supplementation, but individual responses to supplementation vary. We aimed to examine genetic and non-genetic determinants of change in serum 25-hydroxyvitamin D [25(OH)D] following supplementation.

Design and participants: We used data from a pilot randomised controlled trial in which 644 adults aged 60-84 years were randomly assigned to monthly doses of placebo, 30,000 IU, or 60,000 IU vitamin D3 for 12 months. Baseline characteristics were obtained from a self-administered questionnaire. Eighty-eight single nucleotide polymorphisms (SNPs) in 41 candidate genes were genotyped using Sequenom MassArray technology. Serum 25(OH)D levels before and after the intervention were measured using the Diasorin Liaison platform immunoassay. We used linear regression models to examine associations between genetic and non-genetic factors and change in serum 25(OH)D levels.

Results: Supplement dose and baseline 25(OH)D level explained 24% of the variability in response to supplementation. BMI, self-reported health status and ambient UVR made a small additional contribution. SNPs in CYP2R1, IRF4, MC1R, CYP27B1, VDR, TYRP1, MCM6 and HERC2 were associated with change in 25(OH)D level, although only CYP2R1 was significant after adjustment for multiple testing. Models including SNPs explained a similar proportion of variability in response to supplementation as models that included personal and environmental factors.

Conclusion: Stepwise regression analyses suggest that genetic variability may be associated with response to supplementation, perhaps suggesting that some people might need higher doses to reach optimal 25(OH)D levels, or that there is variability in the physiologically normal level of 25(OH)D.

PMID: 24694335

Patients (but not VitaminDWiki) can obtain a free copy of the study from the publisher

See also VitaminDWiki

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