Association of miR-499, miR-27a, and miR-34a Gene Polymorphisms With Susceptibility to Type 2 Diabetes Mellitus in an Iranian Population: A Case-Control Study.

BACKGROUND: Type 2 diabetes mellitus (T2DM) is a multifactorial metabolic disorder influenced by both environmental and genetic factors. MicroRNAs (miRNAs) are involved in the regulation of insulin signaling, inflammation, and pancreatic β-cell function. Genetic polymorphisms in miRNA-related regions may contribute to interindividual differences in T2DM susceptibility, although their functional effects remain uncertain. OBJECTIVE: This study is aimed at evaluating the association of five miRNA polymorphisms, miR-499 rs3746444, miR-27a rs895819/rs895519, miR-34a rs6577555, miR-124a rs531564, and miR-146a rs2910164, with susceptibility to T2DM in an Iranian population. METHODS: This case-control study included 200 patients with T2DM and 202 unrelated healthy controls from southeastern Iran. Genotyping was performed using T-ARMS-PCR and PCR-RFLP methods. Genotype and allele distributions were compared between groups, Hardy-Weinberg equilibrium was assessed in controls, and crude odds ratios (ORs) were calculated under different genetic models. Multivariable logistic regression was also performed to estimate age- and sex-adjusted ORs. Bonferroni correction was applied to account for multiple comparisons. RESULTS: Significant associations with increased T2DM risk were observed for miR-499 rs3746444 C allele (OR = 1.79, 95% CI = 1.34-2.39; p < 0.001), miR-27a rs895819 G allele (OR = 1.89, 95% CI = 1.43-2.51; p < 0.001), and miR-34a rs6577555 A allele (OR = 2.91, 95% CI = 2.19-3.88; p < 0.001). These associations remained evident in age- and sex-adjusted codominant logistic regression models. In contrast, miR-124a rs531564 and miR-146a rs2910164 were not significantly associated with T2DM risk. CONCLUSION: The findings suggest that miR-499 rs3746444, miR-27a rs895819/rs895519, and miR-34a rs6577555 polymorphisms are associated with T2DM susceptibility in this Iranian population. However, these results indicate association rather than causation, and further large-scale, multiethnic, and functional studies are needed to confirm their biological and clinical relevance.