Association of CYP2R1 gene polymorphisms with type 2 diabetes mellitus in the Jordanian population.

BACKGROUNDS: Vitamin D (VD) has been widely reported to be associated with the developing of diabetes, potentially through its effects on insulin sensitivity and glucose homeostasis. In this study, we investigated the association between Single nucleotide polymorphisms (SNPs) in genes that are linked to VD pathway (rs10741657 and rs1074165 in CYP2R1, rs6013897 in CYP24A1, and rs10877012 in CYP27B1) and the risk of type 2 diabetes mellitus (T2DM) in the Jordanian population. METHODS: A total of 200 patients with T2DM and 195 healthy controls were included. SNPs analysis was performed using T-ARMS-PCR. RESULTS: Significant differences in genotype and allele frequencies were observed between patients with T2DM and controls for CYP2R1 rs10741657 and rs1074165 (P < 0.001 and P < 0.01, respectively). The rs10741657 AG genotype (OR = 3.69, 95% CI: 2.27-6.00) and G allele (OR = 2.59, 95% CI: 1.77-3.77) were associated with increased T2DM risk. Similarly, the rs1074165 GA genotype (OR = 4.27, 95% CI: 2.22-8.22) and A allele (OR = 4.68, 95% CI: 2.51-8.72) were significantly associated with T2DM susceptibility. No significant associations were identified for CYP24A1 rs6013897 or CYP27B1 rs10877012. Logistic regression confirmed significant associations between CYP2R1 polymorphisms and T2DM, with rs10741657 AG carriers exhibiting over six-fold higher odds of T2DM (OR = 6.12, 95% CI: 3.08-12.13, P < 0.001). Genetic model analyses further supported the association of both CYP2R1 polymorphisms with T2DM under codominant, dominant, and overdominant inheritance models, whereas no significant associations were observed for CYP24A1 or CYP27B1. CONCLUSION: These findings suggest that CYP2R1 polymorphisms may serve as potential genetic markers for assessing T2DM risk in the Jordanian population.