Wenquan Niu1, Yue Qi. 1. State Key Laboratory of Medical Genomics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. niuwenquan@yahoo.cn
Abstract
CONTEXT AND OBJECTIVE: The association between matrix metalloproteinase (MMP) family gene polymorphisms and coronary artery disease (CAD) has been widely evaluated; however, the studies have yielded contradictory results. The authors sought to investigate this inconsistency by performing a comprehensive meta-analysis on MMP family genes. DATA SOURCES: Articles were identified by searches of PubMed, HuGE Navigator, EMBASE, Wanfang, and China Biological Medicine databases before January 2012, and by hand searches of bibliographies of retrieved articles and reviews. STUDY SELECTION: Qualified articles were retrospective or nested case-control studies of MMP family gene polymorphisms and CAD. A total of 11 polymorphisms from five MMP family genes were meta-analysed. Forty-eight articles encompassing 59 studies fulfilled the predefined criteria. DATA EXTRACTION: Data were independently extracted from qualified articles by two reviewers using a standardized Excel template and were verified. Any disagreement was adjudicated by discussion and a consensus was reached. RESULTS: Overall significant associations were observed for Glu45Lys in MMP3 gene under both allelic (OR: 1.52; 95% CI 1.3 to 1.76; p<0.001) and dominant (1.37; 1.23 to 1.54; <0.001) models, and for -1562C/T in MMP9 gene under allelic model (1.11; 1.02 to 1.2; 0.012). Subgroup analyses demonstrated that sources of study heterogeneity stemmed from the CAD endpoint for -519A/G, -1612 6A/5A, Glu45Lys, from the descent of study populations for -1607GG/G, -1612 6A/5A, -790T/G, -1562C/T, from the study design for -1607GG/G, -1612 6A/5A, -1562C/T, and from the selection of controls for -1306C/T, -1562C/T, Arg279Gln. In meta-regression analyses, effect of -1612 6A/5A on CAD was ethnicity-specific (coefficient: 0.21; p=0.048), and this effect was more prominent for myocardial infarction patients or East Asians. CONCLUSIONS: The results provided strong evidence regarding the susceptibility of MMP3 and MMP9 genes to the development of CAD. Future studies incorporating gene-gene and gene-environment interactions are encouraged.
CONTEXT AND OBJECTIVE: The association between matrix metalloproteinase (MMP) family gene polymorphisms and coronary artery disease (CAD) has been widely evaluated; however, the studies have yielded contradictory results. The authors sought to investigate this inconsistency by performing a comprehensive meta-analysis on MMP family genes. DATA SOURCES: Articles were identified by searches of PubMed, HuGE Navigator, EMBASE, Wanfang, and China Biological Medicine databases before January 2012, and by hand searches of bibliographies of retrieved articles and reviews. STUDY SELECTION: Qualified articles were retrospective or nested case-control studies of MMP family gene polymorphisms and CAD. A total of 11 polymorphisms from five MMP family genes were meta-analysed. Forty-eight articles encompassing 59 studies fulfilled the predefined criteria. DATA EXTRACTION: Data were independently extracted from qualified articles by two reviewers using a standardized Excel template and were verified. Any disagreement was adjudicated by discussion and a consensus was reached. RESULTS: Overall significant associations were observed for Glu45Lys in MMP3 gene under both allelic (OR: 1.52; 95% CI 1.3 to 1.76; p<0.001) and dominant (1.37; 1.23 to 1.54; <0.001) models, and for -1562C/T in MMP9 gene under allelic model (1.11; 1.02 to 1.2; 0.012). Subgroup analyses demonstrated that sources of study heterogeneity stemmed from the CAD endpoint for -519A/G, -1612 6A/5A, Glu45Lys, from the descent of study populations for -1607GG/G, -1612 6A/5A, -790T/G, -1562C/T, from the study design for -1607GG/G, -1612 6A/5A, -1562C/T, and from the selection of controls for -1306C/T, -1562C/T, Arg279Gln. In meta-regression analyses, effect of -1612 6A/5A on CAD was ethnicity-specific (coefficient: 0.21; p=0.048), and this effect was more prominent for myocardial infarctionpatients or East Asians. CONCLUSIONS: The results provided strong evidence regarding the susceptibility of MMP3 and MMP9 genes to the development of CAD. Future studies incorporating gene-gene and gene-environment interactions are encouraged.