ALLELE-SPECIFIC INCREASE IN BASAL TRANSCRIPTION OF THE PLASMINOGEN-ACTIVATOR INHIBITOR-1 GENE IS ASSOCIATED WITH MYOCARDIAL-INFARCTION

Increased plasminogen-activator inhibitor 1 (PAI-1) activity is a comm on finding in patients with coronary heart disease. Here we provide ev idence for an independent, etiological role of PAI-1 in myocardial inf arction, The 4G allele of a recently described common 4/5-guanine-trac t (4G/5G) polymorphism in the PAI-1 promoter is associated with higher plasma PAI-1 activity. The prevalence of the 4G allele is significant ly higher in patients with myocardial infarction before the age of 45 than in population-based controls (allele frequencies of 0.63 vs, 0.53 ), Both alleles bind a transcriptional activator, whereas the 5G allel e also binds a repressor protein to an overlapping binding site. In th e absence of bound repressor, the basal level of PAI-1 transcription i s increased.