Genetic variants within the vitamin D receptor (VDR) gene can significantly modify associations between serum 25-hydroxyvitamin D concentrations and major health outcomes. The study, published in the Nov. 14 issue of the Journal of the American Medical Association, suggests that a personalized clinical approach may be necessary in evaluating serum vitamin D levels as a modifiable risk factor for common health outcomes because of variants affecting downstream 25-hydroxyvitamin D metabolism. “Genetic variation within the vitamin D receptor could alter associations of 25-hydroxyvitamin D concentrations with disease outcomes,” write the authors, led by Gregory Levin, Ph.D., from the University of Washington, Seattle. “Further studies are needed to confirm these observed associations and to enhance knowledge of how variation in vitamin D metabolism genes may stratify individuals as to their susceptibility to vitamin D deficiency.” In a discovery cohort, the researchers studied 141 single-nucleotide polymorphisms (SNPs) found in 1,514 white participants of the Cardiovascular Health Study with no known prevalent cancer, cardiovascular disease, or hip fracture. Replication meta-analyses were conducted, applying the discovered variants across data from three additional studies of more than 2,700 participants. The researchers found that over 11 years of follow-up in the discovery cohort, 948 participants (63 percent) […]
Genetic variants within the vitamin D receptor (VDR) gene can significantly modify associations between serum 25-hydroxyvitamin D concentrations and major health outcomes. The study, published in the Nov. 14 issue of the Journal of the American Medical Association, suggests that a personalized clinical approach may be necessary in evaluating serum vitamin D levels as a modifiable risk factor for common health outcomes because of variants affecting downstream 25-hydroxyvitamin D metabolism.
“Genetic variation within the vitamin D receptor could alter associations of 25-hydroxyvitamin D concentrations with disease outcomes,” write the authors, led by Gregory Levin, Ph.D., from the University of Washington, Seattle. “Further studies are needed to confirm these observed associations and to enhance knowledge of how variation in vitamin D metabolism genes may stratify individuals as to their susceptibility to vitamin D deficiency.”
In a discovery cohort, the researchers studied 141 single-nucleotide polymorphisms (SNPs) found in 1,514 white participants of the Cardiovascular Health Study with no known prevalent cancer, cardiovascular disease, or hip fracture. Replication meta-analyses were conducted, applying the discovered variants across data from three additional studies of more than 2,700 participants.
The researchers found that over 11 years of follow-up in the discovery cohort, 948 participants (63 percent) experienced a composite outcome-defined event. Consistent with previous studies, there was evidence of a threshold association between serum 25-hydroxyvitamin D levels and higher risk of the composite outcome that remained significant even after adjusting for age and sex.
Of the five variants identified in the discovery cohort, only the VDR SNP rs7968585 significantly modified the association between low 25-hydroxyvitamin D concentration and risk of the composite outcome in the independent replication meta-analyses. However, an additional VDR SNP (rs2239179) significantly modified the low 25-hydroxyvitamin D–disease association in a meta-analysis that included both the discovery and replication cohorts. The two identified VDR variants are common SNPs, with minor allele frequencies of 0.48 and 0.42, respectively.
“These results suggest that individuals with specific 25-hydroxyvitamin D metabolism genotypes may be particularly susceptible to, or protected from, the potential adverse health effects of low vitamin D,” write the authors. “The VDR, a member of the steroid-receptor gene superfamily, plays a central role in mediating vitamin D signaling.”
