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
Abstract
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.