Abstract
The present study aimed at investigating the 4G/5G and -844G/A polymorphisms and plasma concentration of PAI-1 in patients with acute myocardial infarction (AMI) and chronic stable angina (CSA) in Indian population. It included 100 patients with AMI and stable angina and 100 healthy controls. All study subjects were typed for two PAI polymorphisms (4G/5G and -844G/A) through PCR-RFLP and level of PAI through ELISA. The comparison of AMI and CSA independently with control in terms of PAI-1 level was statistically significant but not between AMI and CSA. The frequency of 4G/4G and 4G/5G genotype and 4G allele was significantly higher in AMI cases than in control and was found to increase the risk of AMI. There was a significant relationship between 4G/5G polymorphism and AMI risk under the dominant and codominant genotype. The frequency of 4G/4G genotype and 4G allele was significantly higher in CSA cases than in control group and increases the risk of CSA. There was no significant association between 4G/5G polymorphism and CSA risk under recessive, dominant, and codominant models. The genotype and allelic frequencies difference between the cases (AMI and CSA) and control with regard to -844G/A polymorphisms were statistically nonsignificant. Also, we did not detect any significant association of -844G/A polymorphism with AMI and CSA in recessive, dominant, and codominant models. Along with the traditional risk factors, the 4G/5G allele polymorphism is an independent risk factor for the development of AMI. The detection of 4G/5G allele may therefore be helpful in primary prevention. Patients who carry the 4G/5G allele polymorphism have high concentrations of PAI-1, which might be involved in incidents leading to AMI. The present study for the first time revealed significant association of 4G/5G allele polymorphism with high risk of AMI in Indian population and will be helpful in identifying the genetic risk factors associated with AMI and CSA and for better management of diagnostic measures.
Highlights
Atherothrombotic changes are one of the major causes of cardiovascular morbidity and mortality
A single guanosine deletion/insertion polymorphism (4G or 5G) located in the promoter region of the Plasminogen activator inhibitor-1 (PAI-1) gene at 675 base pair upstream from the transcription-starting site has a functional role in PAI-1 synthesis and expression [4]. e PAI-1 level is noted to be higher in 4G allele carrier as compared to 5G carrier, as both polymorphic alleles bind to transcription activator, whereas 5G binds a repressor protein to an overlapping binding site [5]
History of Coronary artery disease (CAD) has been detected in 21% and 23% of acute myocardial infarction (AMI) and chronic stable angina (CSA) cases, respectively
Summary
Atherothrombotic changes are one of the major causes of cardiovascular morbidity and mortality. Plasminogen activator inhibitor-1 (PAI-1) is one of vital regulatory elements of fibrinolytic pathway. It inhibits both tissue and urokinase specific plasminogen inhibitor; its raised level seems to promote prothrombotic state and related vascular changes [3]. E PAI-1 level is noted to be higher in 4G allele carrier as compared to 5G carrier, as both polymorphic alleles bind to transcription activator, whereas 5G binds a repressor protein to an overlapping binding site [5]. PAI-1 4G/5G gene polymorphism is believed to unmask thrombotic phenotype in patients with underlying prothrombotic disorders in both arterial and venous beds such as protein S deficiency, factor V Leiden defect, and antiphospholipid antibody syndrome [6,7,8]. Numerous studies have already been conducted to evaluate the possible sequel of PAI-1 4G/5G gene polymorphism; they reported only conflicting results
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