Genetic determinants of response to vitamin D supplementation.

BACKGROUND

Genetic variants at the vitamin D binding protein (GC), cytochrome P450 family 2 subfamily R member 1 (CYP2R1), and 7-dehydrocholesterol reductase (DHCR7) loci have been associated with serum 25-hydroxy vitamin D (25(OH)D) concentration, but their role in interpreting the response to vitamin D supplementation is unclear. Here, we investigated associations between common variants at these loci and plasma 25(OH)D concentrations in a randomised dose-ranging trial of vitamin D supplementation in healthy older people.

METHODS

The study involved 323 participants of the Vitamin D supplementation in Older People (VDOP) trial, randomly assigned to either 12,000, 24,000, or 48,000 IU colecalciferol monthly for 12 months. Plasma 25(OH)D concentrations were measured by liquid chromatography-mass spectrometry. Variants rs7041 and rs2282679 (GC), rs10741657 (CYP2R1), and rs12785878 (DHCR7) were genotyped by Sanger sequencing. Associations between genotype and 25(OH)D at baseline and post-supplementation were assessed by linear regression analysis with baseline 25(OH)D as a covariate and dose as fixed factor for post-supplementation data.

RESULTS

At baseline, plasma 25(OH)D concentration was associated with the minor allele rs7041-A (GC). Post-supplementation, an allele-dose effect was observed with two variants at the GC locus. Common homozygotes for rs2282679 and rs7041 had higher 25(OH)D concentrations at all supplement dosages, with lower frequency of 25(OH)D concentrations <50 nmol/L compared to other genotypes (OR(95%CI) = 2.97(1.56-5.65) and 2.84(1.28-6.32), respectively).

CONCLUSION

Common genetic variants at the GC locus influence plasma 25(OH)D concentrations and the response to vitamin D supplementation. Genotyping of GC may aid interpreting 25(OH)D concentrations in people who are undergoing supplementation.