A case control study of deep venous thrombosis in relation to factor V G1691A (Leiden) and A4070G (HR2 Haplotype) polymorphisms

Activated protein C resistance (APCR) is a significant risk factor for venous thromboembolism (VTE), with the factor V (FV) G1691A (Leiden) mutation accounting for the majority of inherited APCR cases. An additional FV polymorphism, A4074G (FV-HR2), reportedly increased VTE risk by some, but not all groups. We determined the prevalence of FV-Leiden and FV-HR2 SNPs in 126 patients with deep venous thrombosis (DVT), and 197 control subjects. Frequencies of FV-Leiden A and HR2 G alleles, together with FV-Leiden G/A and A/A (but not HR2 A/G) genotypes were significantly higher among patients. While no significant linkage disequilibrium was noted between FV 1691A and 4070G or A alleles, significantly higher prevalence of single-mutant 1691G/4070G and 1691A/4070A haplotypes were seen in patients. FV Leiden and FV HR2 haplotype are independent risk factors for DVT, and their coinheritance does not seem to increase significantly DVT risk imparted by either.