Researchers recently identified two genes, CYP2R1 and GC, that appear to play an important role in regulating serum 25(OH)D (25-hydroxy vitamin D) concentration, which is an indicator of vitamin D status, in healthy white individuals.

The investigators explained that vitamin D deficiency is related to a number of bone diseases, such as osteoporosis. They noted that genetic factors have been shown to affect serum 25(OH)D levels, but the genes that contribute to the wide variation in these levels have not been elucidated.

To examine the association between genes and variations in 25(OH)D concentration, the researchers conducted a cross-sectional discovery study in which they evaluated nine prominent gene candidates, and then they performed a replication study in a separate cohort to confirm the results.

The discovery cohort included 156 healthy, unrelated, non-Hispanic white adults. Nine candidate genes were selected for assessment, all of which have demonstrated in prior studies involvement with synthesizing, transporting or degrading vitamin D or activating downstream signaling pathways for vitamin D. The candidate genes were screened using 49 SNP (single nucleotide polymorphism) markers, and 46 were successfully genotyped and used for the analysis.

After adjusting for potential confounding factors, including age, sex, body mass index, vitamin D supplementation and the time of year blood was collected, the analysis revealed that six SNPs—four in the CYP2R1 gene (cytochrome P450, family 2, subfamily R, polypeptide 1) and two in the GC gene (vitamin D binding protein)—were significantly associated with serum 25(OH)D levels.

For the replication study, a separate cohort of 340 healthy, unrelated, non-Hispanic white adults was used to evaluate the six SNPs identified in the discovery study. Using the same statistical methodology as in the discovery study, the researchers reported that the findings of the replication study's association analyses showed that two of the SNPs in the CYP2R1 gene were confirmed as being significantly associated with serum 25(OH)D levels, while one of the SNPs in the GC gene was confirmed to be marginally, although still statistically significantly, associated with these levels.

A pooled analysis using participants from both the discovery and replication cohorts (n=496) revealed that several of the SNPs of the CYP2R1 and GC genes remained significantly associated with serum 25(OH)D concentration.

Regarding the study findings, the investigators emphasized the importance of confirming them in other healthy populations and other races.

The data were published in the November issue of the journal Human Genetics.


Study title: Comprehensive association analysis of nine candidate genes with serum 25-hydroxy vitamin D levels among healthy Caucasian subjects
Authors: Feng-Xiao Bu, et al.