Relationship between Functional miR-143/145 Cluster Variants and Susceptibility to Type 2 Diabetes Mellitus: A Preliminary Case-Control Study and Bioinformatics Analyses.

Purpose: To investigate the link between two variants (rs4705342 and rs4705343) in the promoter of the miR-143/145 cluster with Type 2 diabetes mellitus (T2DM) risk. Methods:A total of 1200 subjects were genotyped using the ARMS-PCR method. Results: The rs4705342 variant enhanced the risk of T2DM under codominant CC (OR = 3.24; 95% CI: 1.89-5.60), recessive TT+TC (OR = 3.02; 95% CI: 1.77-5.17), and dominant TC+CC (OR = 1.35; 95% CI: 1.08-1.71) genetic models. Individuals carrying the C allele of rs4705342 conferred a 1.43 fold increased risk of T2DM. As regards rs4705343, decreased risk of T2DM was observed under codominant TC (OR = 0.53; 95% CI: 0.42-0.67), over-dominant TT+CC (OR = 0.51; 95% CI: 0.40-0.64), and dominant TC+CC (OR = 0.59; 95% CI: 0.48-0.75) models. Haplotype analysis of the variants showed a 1.941-fold increased risk of T2DM regarding the C T combination. Significant associations were noticed between different haplotypes and lipid indices of T2DM patients. There were no notable changes in p-values after adjustment for BMI. Computational analysis revealed that miR143 and/or miR145 target important genes involved in glucose and lipid metabolism. Conclusions: Functional miR-143/145 variants might influence the risk of T2DM. Hence, clarifying the precise regulatory mechanisms of gene expression in the development of T2DM will significantly guide researchers to find a novel target for therapeutic intervention.