Strong Association Between MiRNA Gene Variants and Type 2 Diabetes Mellitus in a Caucasian Population

MicroRNAs (miRNAs), small non-coding RNAs, have emerged as promising diagnostic and prognostic biomarkers for various diseases. However, their role in the pathogenesis of type 2 diabetes mellitus (T2DM) remains insufficiently defined. This case-control study investigated associations between genetic variants in miRNA genes and susceptibility to T2DM in a Greek population. A total of 716 individuals with T2DM and 569 controls (HbA1c < 6.5% and fasting plasma glucose < 126 mg/dL) were included. Genomic DNA was extracted from whole blood and genotyped using the Illumina Infinium PsychArray platform. Polymorphisms in <i>MIR124a</i>, <i>MIR27a</i>, <i>MIR146a</i>, <i>MIR34a</i>, <i>MIRLET7A2</i>, <i>MIR128a</i>, <i>MIR196a2</i>, <i>MIR499a</i>, <i>MIR4513</i>, and <i>MIR149</i> were analyzed, with all SNPs within 20 kb upstream and downstream of each gene assessed. Allele frequencies were compared between cases and controls using PLINK. Significant associations with increased T2DM risk were observed for rs1531212 (OR = 1.375, <i>p</i> = 0.018) in <i>MIR23aHG</i> (containing <i>MIR27a</i>) and rs6120777 (OR = 1.27, <i>p</i> = 0.018) in <i>MYH7B</i>, upstream of <i>MIR499a</i>. Conversely, rs2425012 (OR = 0.794, <i>p</i> = 0.018) upstream of <i>MIR27a</i>, as well as rs883517 (OR = 0.728, <i>p</i> = 0.024) and rs2961920 (OR = 0.80, <i>p</i> = 0.041) upstream of <i>MIR146a</i>, appeared protective. Under the dominant model, two additional associations emerged: rs3746435 (OR = 1.239, <i>p</i> = 0.025) in <i>MYH7B</i> (upstream of <i>MIR499a</i>) and rs3746444 (OR = 1.235, <i>p</i> = 0.046) in <i>MIR499a</i>. In conclusion, this study identifies three novel genetic variants near <i>MIR27a</i> and <i>MIR499a</i> that may influence susceptibility to T2DM. These findings warrant validation in larger cohorts and functional studies to clarify their role in T2DM pathogenesis.