Allele-Specific Increase in Basal Transcription of the Plasminogen-Activator Inhibitor 1 Gene is Associated with Myocardial Infraction

Increased plasminogen-activator inhibitor 1 (PAI-1) activity is a common finding in patients with coronary heart disease. Here we provide evidence for an independent, etiological role of PAI-1 in myocardial infarction. The 4G allele of a recently described common 4/5-guanine-tract (4G/5G) polymorphi...

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Bibliographic Details
Published inProceedings of the National Academy of Sciences - PNAS Vol. 92; no. 6; pp. 1851 - 1855
Main Authors Eriksson, Per, Kallin, Bengt, Ferdinand M. Van't Hooft, Bavenholm, Peter, Hamsten, Anders
Format Journal Article
LanguageEnglish
Published National Academy of Sciences of the United States of America 14.03.1995
Subjects
Alleles
Blood plasma
Congenital heart defects
DNA
Genes
Genotypes
Hep G2 cells
Myocardial infarction
Oligonucleotides
Promoter regions
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Summary:Increased plasminogen-activator inhibitor 1 (PAI-1) activity is a common finding in patients with coronary heart disease. Here we provide evidence for an independent, etiological role of PAI-1 in myocardial infarction. The 4G allele of a recently described common 4/5-guanine-tract (4G/5G) polymorphism in the PAI-1 promoter is associated with higher plasma PAI-1 activity. The prevalence of the 4G allele is significantly 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 allele also binds a repressor protein to an overlapping binding site. In the absence of bound repressor, the basal level of PAI-1 transcription is increased.
ISSN:0027-8424
1091-6490