Association between matrix metalloproteinase family gene polymorphisms and risk of ischemic stroke: A systematic review and meta-analysis of 29 studies

Background: Ischemic stroke (IS) is a complex and devastating vascular disease that has become one of the leading causes of disability and mortality worldwide. Several studies have shown the association between matrix metalloproteinase (MMP) family gene polymorphisms and IS. However, the results have been indecisive.

Objective: To investigate the association between Matrix Metalloproteinase gene polymorphisms and risk of IS.

Methods: A literature search for eligible candidate gene studies published before, 28 June 2017, was conducted in the PubMed, EMBASE, Cochrane and Google Scholar databases. The following combinations of main keywords were used: ('Matrix Metalloproteinase' or 'MMP' or 'Stromelysin-1' or 'Gelatinase b') AND ('ischemic stroke' or 'IS') AND ('single nucleotide polymorphism' or 'gene polymorphism' or 'SNP'). Fixed or random effects models were used to estimate the Pooled Odds ratio (OR) and 95% confidence interval (CI). Statistical analysis was carried out by using STATA version 13.0 software.

Results: Total 29 studies were included in our meta-analysis. A significant association was observed for MMP-9 (-1562C/T) (OR 1.27; 95% CI 1.06 to 1.53; p value = 0.01) and MMP-12 (-1082 A/G) (OR 2.55; 95% CI 1.75 to 3.71; p value<0.001) gene polymorphisms and risk of IS. No significant association was found for any of the MMP-1(-1607 1G/2G), MMP-2 (-1306C/T) & (-735C/T) and MMP-3 (-1612 5A/6A) gene polymorphisms with the risk of IS.

Conclusion: Our meta-analysis suggests that MMP-9 (-1562C/T) and MMP-12 (-1082 A/G) gene polymorphisms could be a risk factor for IS while MMP-1 (-1607 1G/2G), MMP-2 (-1306C/T) & (-735C/T) and MMP-3 (-1612 5A/6A) have no association with the risk of causing IS. However, large prospective studies with sufficient power are required to validate our findings.