The A -844G polymorphism in the PAI-1 gene is associated with a higher risk of venous thrombosis in factor V Leiden carriers.

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.