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PAI-1 4G/5G polymorphism and plasma levels association in patients with coronary artery disease
Luciana Moreira Lima1, Maria das Graças Carvalho, Cirilo Pereira Fonseca Neto
1Departamento de Medicina e Enfermagem, Universidade Federal de Viçosa, Viçosa, MG, Brazil. lucianamoreiralima@yahoo.com.br
Insights
The 4G/4G genotype of plasminogen activator inhibitor-1 (PAI-1) is linked to higher PAI-1 levels and severe coronary artery disease (CAD) in Brazilian individuals. Further research is needed to determine if high PAI-1 causes or results from atherosclerosis.
Area of Science:
- Genetics and Cardiovascular Disease
- Molecular Biology and Atherosclerosis
- Clinical Research in Cardiology
Background:
- Type-1 plasminogen activator inhibitor (PAI-1) 4G/5G polymorphism influences PAI-1 expression.
- Elevated plasma PAI-1 levels are a known risk factor for coronary artery disease (CAD).
Purpose of the Study:
- To investigate the impact of PAI-1 4G/5G polymorphism on plasma PAI-1 levels.
- To assess the association between PAI-1 polymorphism, PAI-1 levels, and CAD severity determined by coronary angiography.
Main Methods:
- Genotyping of PAI-1 4G/5G polymorphism using PCR with allele-specific primers.
- Quantification of plasma PAI-1 levels via ELISA assay.
- Analysis of blood samples from patients with varying degrees of coronary stenosis and healthy controls.
Main Results:
- The 4G/4G genotype and higher plasma PAI-1 levels were significantly more prevalent in the severe atheromatosis group.
- Individuals with the 4G/4G genotype exhibited significantly higher plasma PAI-1 levels compared to the 5G/5G genotype.
- PAI-1 was independently associated with coronary artery stenosis exceeding 70% in a multivariate analysis.
Conclusions:
- A significant association exists between the 4G/4G genotype, elevated plasma PAI-1, and severe coronary stenosis (>70%) in the studied Brazilian population.
- The causal relationship between high plasma PAI-1 levels and the progression of atherosclerosis requires further investigation.
Background:
Type-1 plasminogen activator inhibitor (PAI-1) 4G/5G polymorphism may influence the PAI-1 expression. High plasma levels of PAI-1 are associated with coronary artery disease (CAD).
Objective:
This study investigated the influence of PAI-1 4G/5G polymorphism on plasma PAI-1 levels and its association with CAD assessed by coronary angiography.
Methods:
Blood sample of 35 individuals with angiographically normal coronary arteries, 31 individuals presenting mild/moderate atheromatosis, 57 individuals presenting severe atheromatosis and 38 healthy individuals (controls) were evaluated. In patients and controls, the PAI-1 4G/5G polymorphism was determined by PCR amplification using allele-specific primers. Plasma PAI-1 levels were quantified by ELISA assay (American Diagnostica).
Results:
No difference was found between groups regarding age, gender and body mass index. Plasma PAI-1 levels and 4G/4G genotype frequency were significantly higher in the severe atheromatosis group compared to the other groups (p<0.001). Furthermore, patients with 4G/4G genotype (r=0.28, p<0.001) had significantly higher plasma PAI-1 levels than those with 5G/5G genotype (r=0.02, p=0.4511). In addition, in a multiple logistic regression model, adjusted for all the other variables, PAI-1 was observed to be independently associated with CAD > 70% (p<0.001).
Conclusion:
The most important finding of this study was the association between 4G/4G genotype, high plasma PAI-1 levels and coronary stenosis higher than 70% in Brazilian individuals. Whether high plasma PAI-1 levels are a decisive factor for atherosclerosis worsening or it is a consequence remains to be established.
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