RT Journal Article
SR Electronic
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
FD European Respiratory Society
SP P3824
VO 44
IS Suppl 58
A1 Tanya Tacheva
A1 Dimo Dimov
A1 Elina Aleksandrova
A1 Atanas Koychev
A1 Maya Gulubova
A1 Tatyana Vlaykova
YR 2014
UL http://erj.ersjournals.com/content/44/Suppl_58/P3824.abstract
AB 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.