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

## TL;DR

This study finds that certain genetic variants in miRNA genes are strongly linked to an increased risk of type 2 diabetes in a Greek population.

## Contribution

The study identifies three novel genetic variants near MIR27a and MIR499a associated with T2DM susceptibility.

## Key findings

- Genetic variants in MIR27a and MIR499a are significantly associated with increased T2DM risk.
- Some SNPs upstream of MIR27a and MIR146a show protective effects against T2DM.
- The findings suggest a potential role for miRNA gene variants in T2DM pathogenesis.

## Abstract

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 MIR124a, MIR27a, MIR146a, MIR34a, MIRLET7A2, MIR128a, MIR196a2, MIR499a, MIR4513, and MIR149 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, p = 0.018) in MIR23aHG (containing MIR27a) and rs6120777 (OR = 1.27, p = 0.018) in MYH7B, upstream of MIR499a. Conversely, rs2425012 (OR = 0.794, p = 0.018) upstream of MIR27a, as well as rs883517 (OR = 0.728, p = 0.024) and rs2961920 (OR = 0.80, p = 0.041) upstream of MIR146a, appeared protective. Under the dominant model, two additional associations emerged: rs3746435 (OR = 1.239, p = 0.025) in MYH7B (upstream of MIR499a) and rs3746444 (OR = 1.235, p = 0.046) in MIR499a. In conclusion, this study identifies three novel genetic variants near MIR27a and MIR499a that may influence susceptibility to T2DM. These findings warrant validation in larger cohorts and functional studies to clarify their role in T2DM pathogenesis.