Matrix metalloproteinase-9 -1562C/T promoter polymorphism confers risk for COPD: a meta-analysis

Lei Chen; Tao Wang; Lian Liu; Yongchun Shen; Chun Wan; Fuqiang Wen

doi:10.1371/journal.pone.0060523

Matrix metalloproteinase-9 -1562C/T promoter polymorphism confers risk for COPD: a meta-analysis

PLoS One. 2013;8(3):e60523. doi: 10.1371/journal.pone.0060523. Epub 2013 Mar 28.

Authors

Lei Chen¹, Tao Wang, Lian Liu, Yongchun Shen, Chun Wan, Fuqiang Wen

Affiliation

¹ Division of Pulmonary Diseases, State Key Laboratory of Biotherapy of China, West China Hospital, West China School of Medicine, Sichuan University, Chengdu, Sichuan, China.

Abstract

Background: 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.

Methods: Published 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.

Results: A 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, significant 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.

Conclusion: This 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.

Publication types

Meta-Analysis
Research Support, Non-U.S. Gov't

MeSH terms

Case-Control Studies
Humans
Matrix Metalloproteinase 9 / genetics*
Odds Ratio
Polymorphism, Single Nucleotide*
Pulmonary Disease, Chronic Obstructive / genetics*
Smoking / genetics

Substances

Matrix Metalloproteinase 9

Grants and funding

This study was supported in part by grants 31000513, 31171103, 81200031, and 81230001 from the National Natural Science Foundation of China. The funders (grants 31000513, 31171103, 81200031, and 81230001 from the National Natural Science Foundation of China) have no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.