BACKGROUND: 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. OBJECTIVES: 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. MATERIALS AND METHODS: 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. RESULTS: 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). CONCLUSIONS: The study suggests MIR25 SNP rs1527423 as a risk factor for COPD in North Indian populations.