Impact of genetic variants in the MMP and ADAM genes towards chronic obstructive pulmonary disease susceptibility and lung function in the North Indian population.

Abstract

Background-: Chronic Obstructive (COPD)pulmonary disease is a significant global health concern, increasingly linked to genetic factors. Airway remodelling in COPD is associated with ADAM33 and MMPs.

Methods-: This study selected SNPs in the protease pathway to evaluate their impact on COPD. A total of 1000 subjects (500 COPD cases and 500 controls) were recruited. Logistic regression calculated odds ratios (ORs) to assess the association between SNPs and COPD risk, and haplotype analysis was performed. SNP interactions were evaluated using Multifactor Dimensionality (MDR) Reduction, and CART analysis identified high-risk subgroups.

Results-: Results indicated a strong association between COPD and MMP9 rs17576 (OR = 2.01, Pc = 0.0012) and ADAM33 rs2280091 (OR = 1.80, Pc = 0.0012). SNP combinations highlighted the significance of rs17576, rs2280091, and rs612709 in increasing COPD risk. MMP9 (rs17576) (Pc = 0.003) and ADAM33 (rs2280091) (Pc = 0.0054) are linked to disease severity and mucus production, respectively. Haplotype analysis showed a single change in rs17576 and rs2280091 SNPs increases COPD risk. MDR and CART analysis confirmed these results, indicating rs3918392, rs17576, rs2280091, and rs3918396 are strongly associated with COPD risk (p < 0.0001).

Conclusion-: The study concludes that rs3918392, rs17576, rs2280091, rs612709, and rs3918396 are linked to COPD risk in the north Indian population, potentially aiding earlier detection, treatment, and prevention.