From Susceptibility to Disease Severity: Re-Discovering the Clinical Role of MMP-12 Genotypes in Asthma

Asthma is a chronic inflammatory airway disorder influenced by genetic and environmental factors. Matrix metalloproteinase-12 (MMP-12) plays a key role in airway remodeling and inflammation, but its genetic contribution to asthma remains unclear. This study investigated the associations of MMP-12 rs2276109 and rs652438 polymorphisms with asthma susceptibility and severity in 198 Taiwanese asthma patients and 453 controls. Genotypes were determined by PCR-RFLP, and odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using logistic regression. Neither MMP-12 rs2276109 nor rs652438 was significantly associated with overall asthma susceptibility. For rs2276109, the CT and CC genotypes yielded ORs of 1.06 (95% CI = 0.56-2.00, p = 0.9913) and 6.98 (95% CI = 0.72-67.59, p = 0.0857), respectively. However, among individuals aged 25-40 years, rs652438 CT and CC genotypes were associated with elevated asthma risk (OR = 1.86, 95% CI = 1.14-3.04, p = 0.0100; OR = 3.60, 95% CI = 1.11-11.65, p = 0.0494). Furthermore, MMP-12 rs652438 was significantly associated with asthma severity under both the CT genotype (OR = 2.32, 95% CI = 1.16-4.62, p = 0.0250) and dominant models (OR = 2.45, 95% CI = 1.28-4.72, p = 0.0106). Although MMP-12 polymorphisms do not appear to influence overall asthma susceptibility, rs652438 may serve as a genetic marker for disease severity and clinical stratification in asthma.