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

Identification of combined generic factors in factor V Leiden carriers is i mportant for a more accurate risk assessment for venous thrombosis (VT). Am ong these individuals, we evaluated the role of polymorphisms of the plasmi nogen activator inhibitor-1 (PAI-1) gene in the thrombophilic phenotype. A total of 382 factor V Leiden carriers were included in the study. This popu lation was divided into 3 groups. Group 1 (n=168) included individuals with a personal history of VT; group 2 (n=140) included individuals without per sonal VT but with a familial history of VT; and group 3 (n=74) included ind ividuals 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 the se 3 groups of individuals. The A -844G allele frequency differed significa ntly among the 3 groups (P=0.048), the A allele being more frequent in pati ents 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 in dividuals. The prevalence of genotype AA carriers was higher in patients wi th 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 g enotype 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 pu lmonary embolism. Concerning the -675 4G/5G polymorphism, no significant di fference was observed among the 3 groups, the 4G allele frequency being 0.5 4 (in group 1), 0.49 (in group 2), and 0.45 (in group 3). These data sugges t a role fur the -A844G PAI-1 gene polymorphism in the thrombophilic phenot ype of factor V Leiden carriers.