Abstract
BackgroundThe role of matrix metalloproteinase (MMP) gene polymorphisms in the development of chronic obstructive pulmonary disease (COPD) has been reported with inconsistent results. This meta-analysis was performed to assess the association of MMP-1 -1607G/GG and MMP-9 -1562C/T promoter polymorphisms with COPD susceptibility.MethodsPublished case-control studies from Pubmed and China National Knowledge Infrastructure (CNKI) databases were retrieved. Data were extracted and pooled odds ratios (OR) with 95% confidence intervals (CI) were calculated.ResultsA total of fourteen case-control studies were included in this meta-analysis. Pooled effect size showed an association of MMP-9 -1562 C/T with the risk of COPD (dominant model: TT+CT vs CC; OR: 1.46; 95% CI: 1.02–2.08; p = 0.04). However, no correlation with COPD was revealed in MMP-1 -1607G/GG polymorphism. When stratified by ethnicity, results indicated MMP-1 -1607G/GG (recessive model: G/G vs G/GG+GG/GG; OR: 1.20; 95% CI: 1.01–1.44; p = 0.04) and MMP-9 -1562 C/T (dominant model; OR: 1.66; 95% CI: 1.01–2.71; p = 0.04) were correlated with COPD susceptibility among Caucasians and Asians respectively. According to source of controls, signifiant association of MMP-9 -1562 C/T (additive model: T vs C; OR:1.71, 95% CI: 1.42–2.07; p<0.00001, and dominant model; OR: 1.92; 95% CI: 1.34–2.76; p = 0.0004) with COPD susceptibility was revealed in the subgroup with smoker-based controls. However, in the aforementioned risk estimates, only the association of MMP-9 -1562 C/T (additive and dominant models) with the risk of COPD in the subgroup with smoker-based controls persisted significantly after Bonferroni correction for multiple testing. Moreover, after excluding the studies without Hardy–Weinberg equilibrium and/or with small sample size, the pooled results were robust and no publication bias was found in this study.ConclusionThis meta-analysis suggests, when using healthy smokers as controls, MMP-9 -1562 C/T, but not MMP-1 -1607 G/GG polymorphism is associated with the risk of COPD.
Highlights
Chronic obstructive pulmonary disease (COPD) is a worldwide disease, characterized by not fully reversible and progressive airflow limitation
The role of matrix metalloproteinase (MMP) gene polymorphisms in chronic obstructive pulmonary disease (COPD) has been suggested [3], no MMP polymorphisms have been reported to be correlated with COPD in recent genome-wide association studies (GWAS) [4]
I) most of the recent GWAS were performed in the Northern European populations with limited population size and no diverse ethnicities [5], ii) SNPs that possibly had significance but not to reach the genome-wide significant level might be covered in GWAS [6]
Summary
Chronic obstructive pulmonary disease (COPD) is a worldwide disease, characterized by not fully reversible and progressive airflow limitation. The role of MMP gene polymorphisms in COPD has been suggested [3], no MMP polymorphisms have been reported to be correlated with COPD in recent genome-wide association studies (GWAS) [4]. The role of matrix metalloproteinase (MMP) gene polymorphisms in the development of chronic obstructive pulmonary disease (COPD) has been reported with inconsistent results. This meta-analysis was performed to assess the association of MMP-1 -1607G/GG and MMP-9 -1562C/T promoter polymorphisms with COPD susceptibility
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