Analyzing the role of genetic variants in microRNAs and its role as a modulator towards Chronic Obstructive Pulmonary disease (COPD) susceptibility in North Indian population.

miRNAs can target numerous genes, with slight expression changes potentially leading to significant alterations in protein-coding gene expression, affecting various biological processes and possibly worsening conditions like COPD. This study examines the link between six miRNA SNPs (MIR605, MIR608, MIR3117, MIR149, MIR499, and MIR25) and COPD risk in a North Indian population and the functional impact of these miRNA-SNPs on COPD-related pathological factors. To assess genotypes, a case-control study was conducted with 323 COPD cases and 350 hospital controls. Logistic regression determined the odds ratio and 95% confidence interval for the SNP-COPD association, with stratified analysis for clinical parameters, symptoms, and risk factors. SNP-SNP interactions were analyzed using combinatorial analysis, MDR, and CART analysis. MIR25 SNP rs1527423 and MIR608 SNP rs4919510 were significantly associated with COPD risk (OR = 6.38; p < 0.0001 and OR = 1.43, p = 0.02, respectively). rs1527423 remained significant in stratified analysis for age (OR = 6.19; pc = 0.0005), gender (males; OR = 5.93; pc < 0.0001), and smoking status (smokers; OR = 5.02; pc = 0.0006). rs4919510 was associated with COPD risk in patients aged ≥ 65 years (OR = 2.38, pc = 0.0054). MIR605 SNP rs2043556 had a protective effect in non-smokers (OR = 0.142; pc = 0.048). MIR3117 SNP rs4655646 was linked to COPD symptoms. Doublet combinations of each SNP with rs1527423 increased COPD risk. CART analysis identified rs1527423 as a critical factor, with the genotypic combination of 149(M)-3117(M; W)-605(M; W)-608(M; H)-25(W) showing the highest COPD risk (OR = 11; p = 0.0445). The study suggests MIR25 SNP rs1527423 as a risk factor for COPD in North Indian populations.