Polymorphisms of Matrix Metalloproteinases (MMP) in COPD

Abstract

ABSTRACTCOPD is a chronic disease of the lung that is characterized by decreased air flow and is associated with abnormal chronic inflammation in the airways and development of extensive tissue remodeling. Matrix metalloproteinases (MMP) comprise a family of proteolytic enzymes capable to degrade practically all components of exstracellular matrix (ECM) and they play a key role in normal physiological processes of development, tissue remodeling and repair, as well as in various pathological conditions. Based on their substrate specificity and structural organization they are subgrouped into collagenases, stromelysins, gelatinases, matrilysins, and membrane-type matrix metalloproteinases.The MMP activity is very strictly controlled at the level of gene transcription, latent zymogene activation, and inhibition by endogenous inhibitors. Most of MMP genes are highly polymorphic with allele-specific effects on transcriptional activity of the corresponding gene or on the enzyme activity.In the current report we attempt to summarize the information about the role of polymorphisms of MMPs in development and progression of COPD. In addition we comment our own data concerning the effect of two promoter polymorphisms: MMP1 -1607insG (1G>2G, rs1799750) and MMP3 -1171insA (5A>6A, rs3025058) on the risk of COPD, which suggest that SNPs do not represent risk factors for development of COPD, but may affect the lung function.