State Key Laboratory of Medical Genomics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Heart. 2012 Oct;98(20):1483-91. doi: 10.1136/heartjnl-2012-302085. Epub 2012 Jun 11.
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.
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.
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 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.
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.
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.
基质金属蛋白酶（MMP）家族基因多态性与冠状动脉疾病（CAD）之间的关联已得到广泛研究；然而，这些研究结果存在矛盾。作者试图通过对 MMP 家族基因进行综合荟萃分析来研究这种不一致性。
文章通过检索 PubMed、HuGE Navigator、EMBASE、万方和中国生物医学文献数据库，检索了 2012 年 1 月之前的文献，并通过检索文章和综述的参考文献进行了手工检索。
合格的文章是 MMP 家族基因多态性与 CAD 的回顾性或嵌套病例对照研究。对五个 MMP 家族基因中的 11 个多态性进行了荟萃分析。共有 48 篇文章涵盖了 59 项研究符合预定标准。
两位评审员使用标准化的 Excel 模板独立地从合格文章中提取数据，并进行验证。任何分歧都通过讨论进行裁决，并达成共识。
在 MMP3 基因的Glu45Lys 中，在等位基因（OR：1.52；95%CI 1.3-1.76；p<0.001）和显性（1.37；1.23-1.54；<0.001）模型下均观察到总体显著关联，在 MMP9 基因的-1562C/T 下在等位基因模型下观察到总体显著关联（1.11；1.02-1.2；0.012）。亚组分析表明，研究异质性的来源源于 -519A/G、-1612 6A/5A、Glu45Lys 的 CAD 终点，-1607GG/G、-1612 6A/5A、-790T/G、-1562C/T 的研究人群下降，-1607GG/G、-1612 6A/5A、-1562C/T 的研究设计，-1306C/T、-1562C/T、Arg279Gln 的对照选择。在多元回归分析中，-1612 6A/5A 对 CAD 的影响具有种族特异性（系数：0.21；p=0.048），并且这种影响在心肌梗死患者或东亚人中更为明显。
结果为 MMP3 和 MMP9 基因对 CAD 的易感性提供了强有力的证据。鼓励进行纳入基因-基因和基因-环境相互作用的未来研究。
