4G/5G polymorphism of plasminogen activator inhibitor-1 (PAI-1) gene, plasma PAI-1 level and cardiovascular risk factors in Thai patients with high risk for coronary artery disease

Abstract

Impaired fibrinolysis due to elevated plasma plasminogen activator inhibitor type-1 (PAI-1) has been shown to be associated with an increased risk of thrombotic events and may also accelerate the atherosclerotic stenosis process.  Since PAI-1 4G/5G polymorphism has been associated with PAI-1 level and the other conventional risk factors for coronary artery disease (CAD), we therefore investigated the associations of the polymorphism, PAI-1 antigen level and the other conventional risk factors for CAD in Thai patients with high risk for CAD. A total of 131 Thai patients who were clinically suspected of having CAD undergoing coronary angiography at the Cardiac Cathecterization Unit at Queen Sirikit Heart Center of the Northeast Hospital, Khon Kaen University, showing less than 50 % stenosis of major coronary arteries were recruited in this study. The polymorphism was determined using multiplex allele-specific polymerase chain reaction whereas PAI-1 antigen level was measured by an ELISA technique. The traditional risk factors for CAD were also evaluated in the study population. The results showed that genotype frequencies of 4G/4G, 4G/5G and 5G/5G were 32.3, 50.4 and 17.3%, respectively. The association between genotype frequencies of the polymorphism and the traditional risk factors for CAD was not found. Interestingly, significantly higher levels of total cholesterol, triglyceride, low density lipoprotein-cholesterol and TC/high density lipoprotein-cholesterol were observed in 4G allele carriers than in homozygous 5G/5G. In addition, those lipid parameters were correlated with plasma PAI-1 levels. The association of PAI-1 level with the polymorphism was investigated and found no significant difference in PAI-1 level among each genotype (4G/4G = 10.1 ± 7.9 ng/mL, 4G/5G = 9.2 ± 6.8 ng/mL and 5G/5G = 8.3 ± 4.4 ng/mL, P = 0.752). In conclusion, the results of this study showed the association of 4G allele and an elevated PAI-1 level with the increased levels of plasma lipid parameters which are risk factors   for CAD. This may suggest that the interaction of these two parameters may increase risk of thrombotic events in Thai patients with high risk of CAD.