title: The 4G/5G polymorphism in the plasminogen activator inhibitor-1 gene is not associated with myocardial infarction.
abstract: 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.
authors.affiliation: Department of Clinical Epidemiology, Leiden University Medical Center, The Netherlands.
authors.forename: C J
authors.initials: CJ
authors.lastname: Doggen
authors.forename: R M
authors.initials: RM
authors.lastname: Bertina
authors.forename: V M
authors.initials: VM
authors.lastname: Cats
authors.forename: P H
authors.initials: PH
authors.lastname: Reitsma
authors.forename: F R
authors.initials: FR
authors.lastname: Rosendaal
mesh_terms: D000328:Adult; D000368:Aged; D000483:Alleles; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000235:genetics*; D017395:Plasminogen Activator Inhibitor 1 / Q000235:genetics*; D017354:Point Mutation; D011110:Polymorphism, Genetic; D012307:Risk Factors
chemical_list: D017395:Plasminogen Activator Inhibitor 1