Elsevier

Thrombosis Research

Volume 103, Issue 2, 15 July 2001, Pages 103-107
Thrombosis Research

REGULAR ARTICLE
PAI-I 4G/5G polymorphism and sudden cardiac death in patients with coronary artery disease

https://doi.org/10.1016/S0049-3848(01)00277-8Get rights and content

Abstract

The 4G/5G polymorphism of the plasminogen activator inhibitor type I (PAI-I) gene is involved in coronary artery disease (CAD), with the highest risk in 4G/4G homozygotes. The role of PAI-I polymorphism in patients suffering from CAD and history of sudden cardiac death (SCD) has not been addressed yet. We studied the frequency distribution of the PAI-I gene to test the hypothesis that the 4G/4G genotype favors myocardial ischemia and, even in the absence of acute infarction, promotes SCD in patients with CAD. Methods: The PAI-I 4G/5G genotypes and PAI-I antigen plasma levels were determined in 97 patients with CAD and a history of SCD treated with an implantable cardioverter defibrillator (ICD) (defibrillator group) comparing to 113 patients with CAD but no history of SCD (control group). Results: The defibrillator group consisted of significantly more 4G/4G homozygotes and higher PAI-I levels than the control group (44% vs. 24%, 173±41 vs. 144±49 ng/ml; P<.01). The carriers of 4G allele had a significantly higher risk for SCD (odds ratio (OR) 1.9) with the highest risk in the 4G/4G genotype (OR 3.6, P<.01). Conclusion: These results suggest that the PAI-I 4G/4G genotype is associated with SCD in patients suffering from CAD.

Section snippets

Sudden Cardiac Death

SCD was defined as death occurring within 1 h of the development of symptoms in a patient previously in stable condition and with no evidence of myocardial damage during the preceding 24 h.

Study Population

A total of 210 Caucasian patients from the same region were selected. Ninety-seven patients with CAD were survivors of SCD with documented ventricular tachycardia and/or ventricular fibrillation not associated with acute myocardial infarction, who successfully underwent cardiopulmonary resuscitation. These

Results

The baseline characteristics of the study groups are summarized in Table 1. There were no significant differences between the two study groups.

Discussion

In survivors of SCD with underlying CAD, electrocardiographic changes or elevated enzyme levels suggestive of acute myocardial cell damage were found in up to 44% of the patients [3], [4]. For the remaining individuals, different mechanisms should be postulated: a transient ischemic episode too short to result in myocardial damage might be assumed.

A reduction of the endogenous fibrinolytic potential is commonly related to increased plasma levels of PAI-I [8], [9], which, in turn, have been

References (17)

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Cited by (36)

  • Impact of PAI-1 4G/5G and C &gt; G polymorphisms in acute ST elevation myocardial infarction and stable angina patients: A single center Egyptian study

    2018, Egyptian Journal of Medical Human Genetics
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    Among these polymorphisms: 4G/5G insertion/deletion polymorphism at −675 bp of the gene promoter, in addition to C > G polymorphism at the 3′untranslated region (UTR) [16]. PAI-1 4G/5G gene polymorphism and the risk of CAD was thoroughly studied with conflicting data; some studies approving its role in the increased risk of CAD [17,18] while others did not [19,20]. This preliminary study aimed at evaluating the possible role of PAI-1 4G/5G and PAI-1C > G polymorphisms in Egyptian patients with CAD compared to a group of non-ischemic patients.

  • Genetics of Sudden Cardiac Arrest

    2008, Progress in Cardiovascular Diseases
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    The 4G/5G polymorphism in the plasminogen activator inhibitor 1 (PAI-1) gene leads to down-regulation of endogenous fibrinolysis through reduced circulating PAI-1 levels. In a subsequent study in the same population as the ACE/AT1 study, Anvari et al53 examined 97 survivors of SCA with underlying CAD and 113 controls with CAD and no ventricular arrhythmias for the 4G/5G variants. The investigators found an increased prevalence of the 4G/4G genotype in those with CAD who survived SCA vs those who had not had an arrhythmic event.

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A part of these data was presented at the American College of Cardiology 48th and North American Society of Pacing and Electrophysiology 20th Annual Scientific Session 1999 in New Orleans and Toronto, respectively.

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