The 4G/5G polymorphism of PAI-1 promoter gene as a risk factor for myocardial infarction: A meta-analysis approach

Background. The 4G allele of the 4G/5G polymorphism in the promoter region of the PAI-1 gene has been recently reported to predict the risk of myocardial infarction (MI) in a small group of young men. Subsequent studies have produced conflicting results. To further evaluate the association of the 4G/5G polymorphism with the risk of MI, we carried out a meta-analysis of all published studies. Methods and Results. Eight retrospective case-control studies on MI patients and a prospective study were considered. In total, 1521 MI cases and 2120 control subjects were analyzed. The overall distribution of genotypes was: 20.4% 5G/5G, 47.1 % 5G/4G and 32.5% 4G/4G in cases and 28.9% 5G/5G, 47.9% 5G/4G and 23.2% 4G/4G in controls. Across all studies, the mean odds ratio for MI was 1.30 (Clgj: 1.08 to 1.57; P=0.005) for 4G/4G versus 5G/5G genotypes and 1.21 (CI95: 1.03 to 1.42; P=0.02) for 5G/4G+4G/4G versus 5G/5G genotypes. The odds ratio appeared to be increased in high risk populations (i.e. with coronary artery stenosis or non-insulin-dependent diabetes) (OR 4G/4G vs 5G/5G: 2.18; CI95: 1.34 to 3.56). Conclusions. This meta-analysis supports an association of the 4G allele with MI risk. The sample size and the design of the studies included in the overview and the light association found with the risk of MI, all call for other prospective, adequately powered studies, conducted separately in low and high risk subjects.