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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2000;20:1387.)
© 2000 American Heart Association, Inc.

Thrombosis

The A -844G Polymorphism in the PAI-1 Gene Is Associated With a Higher Risk of Venous Thrombosis in Factor V Leiden Carriers

P. E. Morange; M. Henry; D. Tregouët; B. Granel; M. F. Aillaud; M. C. Alessi; I. Juhan-Vague

From the Hematology Laboratory–CHU Timone (P.E.M., M.H., M.F.A., M.C.A., I.J.-V.), Marseille; INSERM U525 (D.T.), Paris; and the Department of Internal Medicine (B.G.), CHU Timone, Marseille, France.

Correspondence to Pr I. Juhan-Vague, Laboratory Hematology–CHU Timone, 13385 Marseille Cedex 5, France.

Abstract—Identification of combined genetic factors in factor V Leiden carriers is important for a more accurate risk assessment for venous thrombosis (VT). Among these individuals, we evaluated the role of polymorphisms of the plasminogen activator inhibitor-1 (PAI-1) gene in the thrombophilic phenotype. A total of 382 factor V Leiden carriers were included in the study. This population was divided into 3 groups. Group 1 (n=168) included individuals with a personal history of VT; group 2 (n=140) included individuals without personal VT but with a familial history of VT; and group 3 (n=74) included individuals without VT and with a fortuitous discovery of the factor V Leiden mutation. We compared the genotype distribution of 2 polymorphisms, A -844G and -675 4G/5G, located in the promoter region of the PAI-1 gene among these 3 groups of individuals. The A -844G allele frequency differed significantly among the 3 groups (P=0.048), the A allele being more frequent in patients who suffered from VT (61%) than in subjects without VT (52%, P=0.015), whereas no difference was observed between the 2 groups of asymptomatic individuals. The prevalence of genotype AA carriers was higher in patients with VT (38%) than in asymptomatic individuals (21%, P=0.015), leading to an odds ratio of 1.74 (95% confidence interval, 1.3 to 3.8). Carrying the AA genotype conferred a risk of deep VT of 2.08 (95% confidence interval, 1.28 to 3.40), whereas it did not seem to significantly influence the risk of pulmonary embolism. Concerning the -675 4G/5G polymorphism, no significant difference was observed among the 3 groups, the 4G allele frequency being 0.54 (in group 1), 0.49 (in group 2), and 0.45 (in group 3). These data suggest a role for the -A844G PAI-1 gene polymorphism in the thrombophilic phenotype of factor V Leiden carriers.

Key Words: PAI-1 • genetic polymorphisms • venous thrombosis • factor V Leiden

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