The association of genetic variants of matrix metalloproteinases with abdominal aortic aneurysm: a systematic review and meta-analysis

Context Aberrant matrix turnover is believed to play a key role in the pathogenesis of abdominal aortic aneurysm (AAA). Matrix metalloproteinases (MMPs) and their inhibitors (tissue inhibitor of metalloproteinases; TIMPs) are important enzymes in the control of extracellular matrix remodelling. Objective The aim of this study was to investigate if single nucleotide polymorphisms (SNPs) within MMP and TIMP gene families are associated with the presence of AAA. Data sources We performed a search of MEDLINE and EMBASE databases on the 21st November 2012. Study selection Case-control studies assessing the association of at least one SNP in a MMP or TIMP gene with AAA were included. Data extraction Data were independently extracted by two reviewers. A random effects model was used to calculate combined odds ratios for commonly investigated SNPs according to dominant, recessive and additive inheritance. Results Thirteen studies examining 58 SNPs within 10 different MMP and TIMP genes were identified. Eight SNPs were assessed in at least 3 studies (combined sample size ranging from 141-2191 AAA cases and 340-2013 controls) and included in a meta-analysis. Results on 1258 cases and 1406 controls for MMP3 rs3025058 showed an association with AAA presence; best described by a dominant pattern of inheritance (OR=1.48 95% CI 1.23 - 1.78, p=3.95x10-5). No associations with AAA were identified for other SNPs assessed in this study including rs1799750 (MMP1), rs3918242 (MMP9), rs486055 (MMP10), rs2276109 (MMP12), rs2252070 (MMP13), rs4898 (TIMP1) or rs9619311 (TIMP3). Conclusion A common SNP within the MMP3 promoter region, previously suggested to increase MMP3 expression, appears to be a moderate risk factor for AAA.