The role of «proteolysis-antiproteolysis» system genes in occupational COPD development.

Abstract

COPD is multifactorial disease, in which hereditary predisposition and environmental factors (including work conditions) play an important role. Among the genes associated with possible predisposition to COPD development a group of genes with the expression impacting the activity of “proteolysis-antiproteolysis – MMP2, MM9, TIMP2, A2M, ELN is considered. The main group of 72 underground coal miners with COPD (mean age 53,7±5,8 years, mean work experience – 21,8±4,8 years), and control group of 79 healthy miners (mean age – 48,2±5,6 years, mean work experience – 20,2±4,5 years) were examined. Polymorphism of genes with out bronchopulmonary pathology MMP9, α2M was revealed using PCR with electroforetic detection in agarosegel. Polymorphism of genes TIMP2, MMP2, ELN was revealed using PCR with fluorescent detection (RealTime PCR). By the data of molecular-genetic research among miners with COPD of occupational etiology (main group) and miners without it (control group) there was estabkished a reliable difference for the genotypes:MMP9*СС,TIMP2*GG; MMP9*СС,MMP2*CC,TIMP2*G/G,α2M*IIe/IIe,ELN*Gly/Gly; MMP9*СС,MMP2*CТ,TIMP2*G/G,α2M*IIe/Val,ELN*Gly/Gly; MMP9*СС,MMP2*CС,TIMP2*G/G,α2M*IIe/Val,ELN*Ser/Se; MMP9*СТ,MMP2*CC,TIMP2*G/G,α2M*IIe/IIe,ELN*Gly/Ser. These genotypes are associated with resistance for COPD development in underground coal miners ofUkraine. The obtained results testify to the participation of genes encoding protein synthesis of the system "proteolysantiproteolysis": MMP2, MMP9, TIMP2, A2M, ELN in the formation of genetic predisposition and resistance to the development of COPD of professional etiology in miners, which reveals new opportunities in the prevention of this disease in workers subject to the high concentrations of coal-rock dust.