The factor V HR2 haplotype and the risk of venous thrombosis: a meta-analysis

Background and Objectives: A complex haplotype of factor V gene (FV HR2) has been recently reported. FVHR2 possesses decreased co-factor activity to APC in the degradation of FVIIIa, and an increased ratio of the more procoagulant isoform FV1 compared to FV2. Contrasting results on whether the haplotype induces a significant risk of venous thromboembolism (VTE) have been reported. Design and Methods: It has been surmised that FVHR2 enhances the risk of VTE carried by FV Leiden. We carried out a meta-analysis of the reported studies on the role of HR2 haplotype in inducing a risk of VTE and the influence of the polymorphism on the risk carried by patients with FV Leiden. Results: Eight studies were analyzed for the estimation of the risk of VTE. A total of 338 out of 2,696 cases (12.5%; range 7.8 to 18.5%) and 885 out of 7,710 controls (11.5%; range 8.1 to 12.1%) were HR2 positive. The odds ratio for VTE associated with HR2 haplotype was not statistically significant (OR 1.15; 95% C.I. 0.98-1.36). The OR for the association between FV Leiden and FV HR2 and the risk of VTE in cases and controls was largely heterogeneous as to OR and 95% C.I. and no statistical significant difference was observed. Interpretation and Conclusions: The data from the present meta-analysis suggests that FVHR2 could be a very mild prothrombotic factor. The association of FV Leiden and HR2 haplotype seems not to increase significantly the risk of VTE carried by isolated heterozygosity for FV Leiden. However, well-designed clinical studies are needed to clarify this issue definitely