The Study On Matrix Metalloproteinases And Tissue Inhibitor Of Metalloproteinase Gene Polymorphism In Chronic Obstructive Pulmonary Disease

OBJECTIVE:Chronic obstructive pulmonary disease (COPD) is a chronic respiratory systemdisease that characterized of airflow limitation and resulted from a combination ofpulmonary emphysema and small airway obstruction. Previous studies suggested thatthe balance between matrix metalloproteinases(MMPs) and tissue inhibitor ofmetalloproteinase (TIMPs) may associate with COPD. Anything that influence theimbalance between MMPs and TIMPs on disturbance in the turnover and depositionof pulmonary extracellular matrix could contribute to the structural remodeling andleading to COPD. Among the MMPs that have been widely explored in COPD suchas MMP-1, MMP-9, and MMP-12, but the aim of this study was to investigate therole of MMP2、MMP-3and TIMP2polymorphism in susceptibility and severity ofCOPD.METHODS:A case-control study research was designed,109patients with COPD weredistinguished into two groups based on FEV1values,80healthy volunteers were usedas the control group. The MMP2(-735C/T)、 MMP-3(–11715A/6A) andTIMP2(+853A/G) polymorphism were determined by polymerase chainreaction-restriction fragment length polymorphism (PCR-RFLP).RESULTS:The G allelic frequency of+853A/G TIMP2in COPD(85.8%) were significantlymore represented than controls(75.6%), may represent a risk factor for thedevelopment of COPD(odds ratio(OR)=1.944,95%confidence interval(CI)=1.151~3.284), and the G/G genotype may also increase the risk of COPD(OR=2.250,95%CI=1.215~4.167). But no difference was noted in the genotype distribution betweenCOPD patients and controls in-735C/T MMP2and–11715A/6A MMP-3(p>0.05).However, among patients with severe disease, the6A/6A genotype frequency in–11715A/6A MMP-3were significantly more represented than controls, the6A/6Agenotype may related to the development of severe COPD(OR=2.677,95%CI= 1.177~6.088).CONCLUSIONS:The genetic polymorphism of+853A/G TIMP2is related to the developmentof COPD，compare with the A allelic and other genotypes, the G allelic and G/Ggenotype may represent a risk factor for the development of COPD. We don’t foundthe genetic polymorphism of–735C/T MMP2and–11715A/6A MMP-3wereassociated with the development of COPD, but the6A/6A genotype may related tothe development of severe COPD.