Genetic variants in vitamin D metabolism-related genes are associated with vitamin D status and adiposity markers.

Single nucleotide variants (SNVs) in vitamin D (VD) metabolism genes have been shown to be associated with serum 25(OH)D concentrations. Although these associations have been reported in other populations, they are less studied in Mexico, a country with high vitamin D deficiency (VDD) despite ample sun exposure. Therefore, we investigate the association between VD-metabolism related SNVs, serum 25(OH)D concentrations, and their impact on VDD and adiposity indicators. We hypothesized that SNVs are associated with serum 25(OH)D concentrations in the Mexican population. We included 1977 individuals (597 males and 1380 females) from the Health Worker Cohort Study. Nine genetic variants: rs10741657 (CYP2R1), rs6013897 (CYP24A1), rs10877012 (CYP27B1), rs10783219 and rs4516035 (VDR), rs4588 and rs7041 (GC), rs4944957 and rs3794060 (NADSYN1), in VD metabolism-related genes were genotyped. Linear and logistic regression models were used to assess the association of interest. In our study, 7 genetic variants were associated with serum 25(OH)D concentrations and VDD. A genetic risk score was created using variants rs6013897 (CYP24A1), rs4516035 (VDR), and rs4588 (GC), which were associated with lower serum 25(OH)D concentrations, higher VDD prevalence, and increased odds of VDD. A second GRS using all 9 variants showed weaker associations. Gene-gene interactions between rs3794060-rs4944957 (NADSYN1), and rs10877012(CYP27B1)-rs7041(GC), were associated with serum 25(OH)D concentrations and VDD, respectively. Additionally, SNV interactions with body mass index, waist circumference, and body fat distribution were identified. These findings suggest that SNVs influence serum 25(OH)D concentrations and adiposity indicators, with potential clinical implications for obesity management.