The Correlation Between 4G/5G Polymorphism In Promoter Region Of PAI-1 Gene And Coronary Artery Disease

ObjectivesThis study was designed to examine the association among 4G/5G polymorphism in the promoter region of plasminogen activator inhibltor-1 (PAI-1) gene, plasma PAI-1 activity and coronary artery disease in Han Chinese.MethodsPolymerase chain reaction-Restriction fragment length polymorphism technique (PCR-RFLP) was employed to determine the 4G/5G polymorphism located in the promoter region of PAI-1 gene in 181 patients with CAD and 210 healthy controls, the plasma PAI-1 activity was measured with chromogenic substrate assay. The blood lipid profile, blood pressure, body mass index (BMI) were documented.Results1. The correlation between 4G/5G polymorphism in promoter region of PA!-1 gene and activity of PAI-1 In the three genotypes, average PAI-1 activity was highest in the genotype 4G/4G, following by the genotype 4G/5G, and that of genotype 5G/5G was lowest. The multi-variate step regression analysis showed that the PAI-1 activity was significantly correlated positively to (r=0.51, P<0.001) and mainly determined by PAI-1 genotypes (b'=0.35), though the environmental factors including BMI, total cholesterol, triglyceride also affected the PAI-1 activity.2, The correlation between 4G/5G polymorphism in promoter region PAI-1 gene and acute coronary syndrome (ACS) The frequency of PAI-1 gene 4G/4G polymorphism in patients with ACS was significantly higher than those without ACS (P<0.01). And PAI-1 activities of all three genotypes in patients with ACS were higher than those without ACS, respectively, with asignificant difference of PAI-1 activities between genotypes of 4G/4G and 5G/5G (p<0.05).3. The correlation between 4G/5G polymorphism in promoter region PAI-1 gene and premature coronary artery disease The frequency of PAI-1 gene 4G aliele in patients with premature coronary artery disease was significantly higher than that without premature coronary artery disease and that in healthy controls, respectively (p<0.01, each). There was no significant difference between the PAI-1 activities in patients with and without premature coronary artery disease. However, the PAI-1 activities in patients with and without premature coronary artery disease were higher than those in healthy controls (p<0.05).4. The correlation between 4G/5G polymorphism in promoter region PAI-1 gene and the severity of coronary artery disease With the increment of the severity of coronary artery disease, the frequency of 4G+ increased significantly (p<0.05).Conclusions4G/5G polymorphism in the promoter region PAI-1 gene significantly affects the PAI-1 activity. The premature of coronary artery disease, the predisposition of ACS and the severity of coronary artery disease are influenced by 4G/5G polymorphism with overexpression of PAI-1.