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

Several studies have found an association between high plasminogenactivator inhibitor-1 (PAI-1) levels and myocardial infarction.Whether this is causal or a consequence of atherosclerosis or tissuedamage, remains unclear. Homozygous carriers of the 4G allele of the4G/5G polymorphism in the PAI-1 gene have higher PAI-1 levels comparedto carriers of the 5G allele in healthy persons in some studies, butnot all. If PAI-1 levels are causally related to myocardial infarction, onewould expect more homozygous carriers of the 4G allele among patients,provided that these carriers have high PAI-1 levels among healthypersons in that population. We investigated the distribution of this polymorphismin the "Study of Myocardial Infarctions Leiden" (SMILE),including 331 men with a myocardial infarction and 302 controlsubjects and measured PAI-1 antigen levels among the latter. Secondly,we looked into the association of cardiovascular risk factors withPAI-1 levels.We did not find an increase in risk of myocardial infarction in carriersof the 4G allele. Neither did we find an association, nor a trend,between the 4G/5G polymorphism and PAI-1 antigen levels in controlsubjects. Controls with obesity, hypertension, or who smoked had significanthigher PAI-1 antigen levels compared with persons withoutthese factors. High cholesterol and triglyceride levels were also associatedwith high PAI-1 antigen levels, and HDL-cholesterol levelsshowed an inverse association.We conclude that the 4G/5G polymorphism in the PAI-1 gene is notassociated with the risk of myocardial infarction. As we did not findany association between this polymorphism and PAI-1 antigen levels inhealthy persons, we cannot draw any conclusions about the causality ofPAI-1 itself for myocardial infarctio