The factor V gene A4070G mutation and the risk of venous thrombosis

The A4070G polymorphism in exon 13 of the factor V (FV) gene, which replace s His by Arg at position 1299 of the B domain, was recently shown to influe nce circulating FV levels and to contribute to the activated protein C (APC ) resistance phenotype. We examined the impact of this polymorphism in a po pulation of unselected patients with venous thromboembolic disease (VTE). T he prevalence of the G4070 (R2) allele was determined in 205 patients and 3 94 healthy subjects of similar age and sex distribution. Thirty-seven patie nts (18%) were heterozygous for the R2 allele and 1 (0.5%) was homozygous. Forty-four controls (11.2%) were heterozygous for the R2 allele and 1 (0.2% ) was homozygous. Thus, the allelic frequency was significantly higher in t he patients with VTE than in the healthy controls, with respective values o f 9.5% and 5.8%. The odds ratio was 1.8 (95% CI: 1.1-2.8, p = 0.02), pointi ng to an increased risk of VTE in carriers of the R2 allele. After excludin g subjects with putative or confirmed gene defects (mainly the FV R506Q mut ation), the R2 allele was still a risk factor for VTE in the remaining pati ents, with an odds ratio of 2.0 (95% CI: 1.2-3.5, p = 0.01), demonstrating that this polymorphism is itself a risk factor. This study also confirms th at the R2 allele influences APC resistance (APCR) in the absence of the FV R506Q mutation.