The plasminogen activator inhibitor-1 (pai-1) gene locus 4g/5g polymorphism and Pai-1 plasma levels in Egyptian patients with myocardial infarction

Abstract

Activation of inflammation and coagulation are closely related andmutually interdependent in myocardial infarction (MI). The acute-phaseprotein, plasminogen activator inhibitor-1 (PAI-1), is a key element in theinhibition of fibrinolysis. Elevated levels of PAI-1 have been related toMI. There are controversial data regarding the impact of 4G/5Gpolymorphism of the PAI-1 gene in the pathogenesis of MI. Patients withMI exhibited significantly higher plasma PAI-1 levels than controls.Significant changes in PAI-1 levels were found in homozygous PAI-14G/4G carriers compared with other 4G/5G genotype carriers in patientswith MI. The allelic frequency of 4G among the patients was 83.3%; thatof 5G was 16.7%. In the control group, the allelic frequencies of 4G and5G were 62.0% and 38.0% respectively. The difference in genotypedistribution between the two groups was significant. There weresignificant associations between MI and the 4G allele, hypertension,smoking, and family history of coronary heart disease. Our findingssuggest that the 4G allele of the PAI-1 promoter polymorphism is anindependent risk factor for MI. The emerging evidence that circulatinglevels of PAI-1 relate to genotype at a common polymorphism in thepromoter of the PAI-1 gene has opened the possibility of using PAI-1 genotype as a surrogate measure of pre-morbid PAI-1 levels to teaseapart the cause and effect limbs of the PAI-1-coronarydiseaserelationship. The detection of this allele along with other risk factors maytherefore be useful in primary prevention.Keywords: Myocardial infarction, plasminogen activator inhibitor-1,polymorphism, fibrinolysis.