TY - JOUR T1 - -82 A>G promoter polymorphism in the gene of human macrophage elastase (MMP-12) as a risk factor for COPD and bronchial asthma JF - European Respiratory Journal JO - Eur Respir J VL - 44 IS - Suppl 58 SP - P3824 AU - Tanya Tacheva AU - Dimo Dimov AU - Elina Aleksandrova AU - Atanas Koychev AU - Maya Gulubova AU - Tatyana Vlaykova Y1 - 2014/09/01 UR - http://erj.ersjournals.com/content/44/Suppl_58/P3824.abstract N2 - Matrix metalloproteinases (MMP) are a large family of zinc-dependent proteolytic enzymes which have a pivotal role in many physiological and pathological conditions due to their ability to cleave the proteins of extracellular matrix and other biologically active proteins. MMP-12 (macrophage elastase) has been shown to be important in abnormal airway inflammation and tissue remodelingin COPD and Bronchial asthma (BA). At least 2 functional polymorphism in the promoter regions of MMP12 have been described as the more common A allele of MMP12 -82 A>G SNP was associated with higher gene expression. In the current study we aimed to explore the possible role of MMP12 -82 A>G SNP in development of COPD and BA. We genotyped 119 control individuals, 167 patients with COPD and 58 with BA for MMP12 -82A>G SNP using PCR-RFLP. The genotype distribution showed statistically significant differences between controls (AA-63.9%, AG-35.5%, GG-0.8%) and patients with COPD (AA-77.8%, AG-19.8%, GG-2.4%, p=0.010) and with BA (AA-86.2%, AG-13.8%, GG-0%, p=0.008). The obtained genotype distributions determined 1.99- fold lower risk of developing COPD (OR=0.50, 95% CI 0.30-0.85, p=0.009) and 3.53-fold lower risk of developing BA (OR=0.28, 95% CI 0.13-0.64, p=0.002) for the carriers of G allele genotypes (AG+GG) compared to the carriers of AA genotype. Based on our results we suggest that the more common A allele and AA genotype of MMP12 -82 A>G promoter polymorphism may be considered as risk factors for developing of COPD and bronchial asthma, possibly by enhancing airway wall degradation and injury due to increased levels of macrophage elastase in carriers of AA genotype. ER -