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=3.95×10-5). 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.