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(Arteriosclerosis, Thrombosis, and Vascular Biology. 1997;17:851-858.)
© 1997 American Heart Association, Inc.

Articles

Five Frequent Polymorphisms of the PAI-1 Gene

Lack of Association Between Genotypes, PAI Activity, and Triglyceride Levels in a Healthy Population

Mireille Henry; Nathalie Chomiki; Pierre Yves Scarabin; Marie Christine Alessi; Franck Peiretti; Dominique Arveiler; Jean Ferrières; Alun Evans; Philippe Amouyel; Odette Poirier; François Cambien; ; Irène Juhan-Vague

From the Laboratoire Hématologie, CJF INSERM 93-12, Marseille (M.H., N.C., M.C.A., F.P., I.J.-V.), and INSERM U 258, Paris (P.Y.S., F.C.), France; The MONICA Projects of Strasbourg, France (D.A.), Toulouse, France (J.F.), Belfast, UK (A.E.), and Lille, France (P.A.); and INSERM SC7, Paris, France (O.P., F.C.).

Correspondence to I. Juhan-Vague, Laboratoire Hématologie, CJF INSERM 93-12, CHU Timone, 13385 Marseille Cedex 5, France.

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 nonisotopic 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.

Key Words: PAI-1 • PCR-SSCP • polymorphism • healthy subjects • PAI activity • metabolic parameters

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