Polymorphisms in metalloproteinase-9 are associated with the risk for asthma in Mexican pediatric patients

Asthma is characterized by chronic airway inflammation, which induces airway remodelling of the extracellular matrix over time. Matrix metalloproteinases (MMPs) are involved in this process, and single-nucleotide polymorphisms (SNPs) in MMP genes may influence their mRNA expression levels or abilities to bind substrates and inhibitors, thereby contributing to asthma predisposition and severity. MMP-9 is highly expressed in airways and many studies support its involvement in asthma pathogenesis; however the contribution of MMP-9 SNPs is controversial. To investigate whether MMP-9 SNPs are associated with childhood-onset asthma in Mexican patients we conducted a case-control study including 403 children with clinical asthma diagnoses and 426 healthy controls from Mexico. The cases and controls were matched by ethnicity and gender. We found that the SNPs rs2274755, rs17577, and rs3918249 were associated with asthma risk. The most significant associations were with rs2274755 (OR = 2.10, 95% CI 1.31–3.39, P = 0.001) and rs17577 (OR = 2.07, 95% CI 1.29–3.30, P = 0.001); which were in strong linkage disequilibrium. Both SNPs were also associated with atopic asthma (OR = 2.38, 95% CI 1.44–3·96, P = 0.0005). The SNP rs3918249 exhibited a female gender-dependent association with asthma (OR = 1.66, 95% CI 1.14–2.43, P = 0.007). Our results suggest that MMP-9 polymorphisms could play a role in the susceptibility to childhood-onset asthma.