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 and
mutually interdependent in myocardial infarction (MI). The acute-phase
protein, plasminogen activator inhibitor-1 (PAI-1), is a key element in the
inhibition of fibrinolysis. Elevated levels of PAI-1 have been related to
MI. There are controversial data regarding the impact of 4G/5G
polymorphism of the PAI-1 gene in the pathogenesis of MI. Patients with
MI exhibited significantly higher plasma PAI-1 levels than controls.
Significant changes in PAI-1 levels were found in homozygous PAI-1
4G/4G carriers compared with other 4G/5G genotype carriers in patients
with MI. The allelic frequency of 4G among the patients was 83.3%; that
of 5G was 16.7%. In the control group, the allelic frequencies of 4G and
5G were 62.0% and 38.0% respectively. The difference in genotype
distribution between the two groups was significant. There were
significant associations between MI and the 4G allele, hypertension,
smoking, and family history of coronary heart disease. Our findings
suggest that the 4G allele of the PAI-1 promoter polymorphism is an
independent risk factor for MI. The emerging evidence that circulating
levels of PAI-1 relate to genotype at a common polymorphism in the
promoter 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 tease
apart the cause and effect limbs of the PAI-1-coronarydisease
relationship. The detection of this allele along with other risk factors may
therefore be useful in primary prevention.

Keywords: Myocardial infarction, plasminogen activator inhibitor-1,
polymorphism, fibrinolysis.