The 4G/5G Polymorphism in the Plasminogen Activator Inhibitor-1 Gene Is not Associated with Myocardial Infarction

C. J. M. Doggen; R. M. Bertina; V. Manger Cats; P. H. Reitsma; F. R. Rosendaal

doi:10.1055/s-0037-1614639

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 1999; 82(01): 115-120
DOI: 10.1055/s-0037-1614639

Rapid Communication

Schattauer GmbH

The 4G/5G Polymorphism in the Plasminogen Activator Inhibitor-1 Gene Is not Associated with Myocardial Infarction

C. J. M. Doggen

¹From the Department of Clinical Epidemiology, Leiden University Medical Center, The Netherlands

,

R. M. Bertina

²From the Hemostasis and Thrombosis Research Center, Leiden University Medical Center, The Netherlands

,

V. Manger Cats

³From the Department of Cardiology, Leiden University Medical Center, The Netherlands

,

P. H. Reitsma^*

²From the Hemostasis and Thrombosis Research Center, Leiden University Medical Center, The Netherlands

,

F. R. Rosendaal

¹From the Department of Clinical Epidemiology, Leiden University Medical Center, The Netherlands

²From the Hemostasis and Thrombosis Research Center, Leiden University Medical Center, The Netherlands

› Author Affiliations

Abstract

Summary

Several studies have found an association between high plasminogen activator inhibitor-1 (PAI-1) levels and myocardial infarction. Whether this is causal or a consequence of atherosclerosis or tissue damage, remains unclear. Homozygous carriers of the 4G allele of the 4G/5G polymorphism in the PAI-1 gene have higher PAI-1 levels compared to carriers of the 5G allele in healthy persons in some studies, but not all. If PAI-1 levels are causally related to myocardial infarction, one would expect more homozygous carriers of the 4G allele among patients, provided that these carriers have high PAI-1 levels among healthy persons in that population. We investigated the distribution of this polymorphism in the “Study of Myocardial Infarctions Leiden” (SMILE), including 331 men with a myocardial infarction and 302 control subjects and measured PAI-1 antigen levels among the latter. Secondly, we looked into the association of cardiovascular risk factors with PAI-1 levels.

We did not find an increase in risk of myocardial infarction in carriers of the 4G allele. Neither did we find an association, nor a trend, between the 4G/5G polymorphism and PAI-1 antigen levels in control subjects. Controls with obesity, hypertension, or who smoked had significant higher PAI-1 antigen levels compared with persons without these factors. High cholesterol and triglyceride levels were also associated with high PAI-1 antigen levels, and HDL-cholesterol levels showed an inverse association.

We conclude that the 4G/5G polymorphism in the PAI-1 gene is not associated with the risk of myocardial infarction. As we did not find any association between this polymorphism and PAI-1 antigen levels in healthy persons, we cannot draw any conclusions about the causality of PAI-1 itself for myocardial infarction.

Full Text

References

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