title: Five frequent polymorphisms of the PAI-1 gene: lack of association between genotypes, PAI activity, and triglyceride levels in a healthy population.
abstract: The main function of plasminogen activator inhibitor type 1 (PAI-1) is to decrease fibrinolysis, which leads to fibrin accumulation. An elevated plasma PAI-1 concentration has been identified as a risk factor for the development of myocardial infarction, and an association between 1 polymorphism of the PAI-1 promoter and plasma PAI-1 levels has been described. Our aim was to identify new polymorphisms in the PAI-1 gene and to further examine the relationship between PAI-1 genotypes and circulating PAI-1 levels. We report the presence of 4 new polymorphisms that were identified by non-isotopic single-strand conformational polymorphism analysis followed by sequencing. These polymorphisms were investigated in relation to PAI-1 levels in a sample of 256 healthy men, aged 50-59 years, from France and Northern Ireland. Two G/A substitutions were detected at positions -844 and +9785. The former is in strong positive linkage disequilibrium with the previously described 4G/5G polymorphism at position -675. Two polymorphisms in the 3' untranslated region were identified. One corresponds to a T/G substitution at position +11,053 and is in negative linkage disequilibrium with the G/A substitution (+9785). The other is a 9-nucleotide insertion/deletion located between nucleotides +11,320 and +11,345 in a threefold-repeated sequence. This polymorphism is in strong positive linkage disequilibrium with the G/A substitution (+9785). The overall heterozygosity provided by the 5 PAI-1 polymorphisms (including the 4 new variants and the 4G/5G polymorphism) was .77. No significant association was found between PAI activity and genotypes; furthermore, the well known associations between PAI activity and body mass index, serum triglycerides, or insulin were homogeneous according to PAI-1 genotypes.
authors.affiliation: Laboratoire Hématologie, CJF INSERM 93-12, Marseille, France.
authors.forename: M
authors.initials: M
authors.lastname: Henry
authors.forename: N
authors.initials: N
authors.lastname: Chomiki
authors.forename: P Y
authors.initials: PY
authors.lastname: Scarabin
authors.forename: M C
authors.initials: MC
authors.lastname: Alessi
authors.forename: F
authors.initials: F
authors.lastname: Peiretti
authors.forename: D
authors.initials: D
authors.lastname: Arveiler
authors.forename: J
authors.initials: J
authors.lastname: Ferrières
authors.forename: A
authors.initials: A
authors.lastname: Evans
authors.forename: P
authors.initials: P
authors.lastname: Amouyel
authors.forename: O
authors.initials: O
authors.lastname: Poirier
authors.forename: F
authors.initials: F
authors.lastname: Cambien
authors.forename: I
authors.initials: I
authors.lastname: Juhan-Vague
mesh_terms: D005602:France; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009660:Northern Ireland; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood / Q000235:genetics*; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D011401:Promoter Regions, Genetic; D017422:Sequence Analysis, DNA; D014280:Triglycerides / Q000097:blood*
chemical_list: D017395:Plasminogen Activator Inhibitor 1; D014280:Triglycerides