Genetic Polymorphism of PAI-1 Gene and Cardiovascular Disease: eta-analysis of Case-Control Studies

ABSTRACT

BACKGROUND: Previous reports have suggested that alleles at the plasminogen activator inhibitor-1 (PAI-1) gene are associated with increased risk of developing coronary artery disease, including myocardial infarction and stroke through their effect on PAI-1 levels. Method: We attempted to search English literatures for all reports of possible effects of PAI-1 gene on cardiovascular disease in human published prior to November 1998. We used a Mantel-Haenszel method (fixed effect model) and random effect model, respectively, to perform a meta-analysis of 7 case-control studies that provided information related to the effects of PAI-1 gene on risk of cardiovascular disease. RESULTS: From 7 studies for diagnosed cardiovascular disease, the relative frequencies of the three genotypes among controls was (5G/5G) (homozygous normal), 24.5%; (4G/5G) (heterozygous), 48.2%, and (4G/4G) (homozygous for the mutant, 675 GGGG), 27.3%. These relative frequencies in cases were 21.7% for 5G/5G, 48.0% for 4G/5G, and 30.3% for 4G/4G. In fixed effect model, compared with those with genotype (5G/5G), the overall odds ratio (OR) for cardiovascular disease among those with (4G/5G) was 1.12 (95% CI, 0.93 to 1.34), and it was 1.20 (1.01 to 1.44) for the (4G/4G) genotype. For five studies with myocardial infarction as the outcome, the overall OR of myocardial infarction was 1.20 (0.99 to 1.47) for those with (4G/5G) and 1.24 (1.00, 1.54) for those with (4G/4G) genotypes, respectively. CONCLUSION: Our findings provide support for the weak association between PAI-1 gene and cardiovascular disease, in particular, myocardial infarction.