Relationships of MMP-9 and TIMP-1 proteins with chronic obstructive pulmonary disease risk: A systematic review and meta-analysis

Background: We performed this meta-analysis in order to collect all the relevant studies to clarify the correlations of matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of metalloproteinase-1 (TIMP-1) with chronic obstructive pulmonary disease (COPD). Materials and Methods: After a literature search in electronic databases, pertinent case-control studies investigating the correlations of MMP-9 and TIMP-1 protein expressions within a COPD setting were enrolled based on our strict inclusion and exclusion criteria. We used key words such as “chronic obstructive pulmonary disease,” “COPD” or “COAD” or “chronic obstructive airway disease” and “matrix metalloproteinases” or “MMPs” to make a searching strategy in this study. STATA software (version 12.0, Stata Corporation, College Station, TX, USA) was utilized for statistical analysis. Results: A total of 20 studies were enrolled into this meta-analysis including 923 COPD patients and 641 healthy controls. The findings of this meta-analysis revealed that serum expression levels of MMP-9 and TIMP-1 protein in COPD patients were higher than those of healthy controls (MMP-9: SMD = 1.44, 95%CI = 0.85 ~ 2.04, P < 0.001; TIMP-1: SMD = 3.53, 95% CI = 2.31 ~ 4.75, P < 0.001). Subgroup analysis based on ethnicity revealed that both Caucasians and Asian COPD patients exhibited higher MMP-9 and TIMP-1 serum protein levels than healthy controls (MMP-9: SMD = 0.81, 95%CI = 0.15~1.48, P = 0.016; TIMP-1: SMD = 4.43, 95%CI = 1.98 ~ 6.87, P = 0.016) and in Caucasians (MMP-9: SMD = 2.30, 95%CI = 1.21 ~ 3.38, P < 0.001; TIMP-1: SMD = 2.86, 95%CI = 1.47 ~ 4.24, P < 0.001). Conclusion: The result of this meta-analysis indicates that elevated levels of MMP-9 and TIMP-1 proteins may be correlated with the pathogenesis of COPD, and the two proteins may represent important biological markers for the early diagnosis of COPD.