title: The A -844G polymorphism in the PAI-1 gene is associated with a higher risk of venous thrombosis in factor V Leiden carriers.
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.
authors.affiliation: Hematology Laboratory-CHU Timone, Marseille, France.
authors.forename: P E
authors.initials: PE
authors.lastname: Morange
authors.forename: M
authors.initials: M
authors.lastname: Henry
authors.forename: D
authors.initials: D
authors.lastname: Tregouët
authors.forename: B
authors.initials: B
authors.lastname: Granel
authors.forename: M F
authors.initials: MF
authors.lastname: Aillaud
authors.forename: M C
authors.initials: MC
authors.lastname: Alessi
authors.forename: I
authors.initials: I
authors.lastname: Juhan-Vague
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D005165:Factor V / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006720:Homozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D017395:Plasminogen Activator Inhibitor 1 / Q000235:genetics*; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D012307:Risk Factors; D020246:Venous Thrombosis / Q000235:genetics*
chemical_list: D017395:Plasminogen Activator Inhibitor 1; C095381:factor V Leiden; D005165:Factor V