SNP rs11185644 of RXRA gene is identified for dose-response variability to vitamin D3 supplementation: a randomized clinical trial.
Level 2 - randomized trial
Individual randomized controlled trial dataset evaluated for pharmacogenetic associations
PubMed 28079136 · doi:10.1038/srep40593
What was done
Researchers evaluated 291 single nucleotide polymorphisms (SNPs) across two randomized clinical trials of vitamin D3 and calcium supplementation in 2,207 healthy postmenopausal Caucasian women. They tested for genetic associations with baseline serum 25-hydroxyvitamin D [25(OH)D] concentrations and with the change in serum 25(OH)D levels following supplementation (dose-response).
What was found
Five SNPs in the *CYP2R1* gene (rs10500804, P = 4.93 × 10⁻⁷; rs2060793, P = 6.63 × 10⁻⁷; rs10741657, P = 1.49 × 10⁻⁶; rs10766197, P = 1.05 × 10⁻⁵; rs11023380, P = 7.67 × 10⁻⁵) and six SNPs in the *GC* gene (rs4588, P = 7.86 × 10⁻⁷; rs2298850, P = 1.94 × 10⁻⁶; rs1155563, P = 6.39 × 10⁻⁶; rs705119, P = 2.80 × 10⁻⁵; rs705120, P = 1.08 × 10⁻⁴; rs222040, P = 1.59 × 10⁻⁴) were significantly associated with baseline serum 25(OH)D levels. A single SNP near *RXRA*, rs11185644, was significantly associated with 25(OH)D dose-response (P = 1.01 × 10⁻⁴). Specific effect sizes or allele frequencies were not reported in the abstract.
Why it matters
The findings identify a genetic contributor (*RXRA* polymorphism) to individual variability in vitamin D treatment response, supporting the biological basis for personalized vitamin D supplementation strategies.
Limits
The study included only healthy postmenopausal Caucasian women, limiting generalizability to males, other age groups, and non-Caucasian populations. The abstract does not provide exact supplementation dosages, intervention duration, or quantitative effect sizes for the identified variants.
Cited by
- supports Certain genetic polymorphisms cause some individuals to require two to three times the normal dose of vitamin D to raise blood levels to 30 to 40 ng/mL.