Factor V R506Q mutation-Leiden: an independent risk factor for venous thrombosis but not coronary artery disease.

BACKGROUND: A specific point G-A transition at nucleotide position 1691 in the factor V (FV) gene, FV-Leiden, was associated with increased risk of venous thromboembolism (VTE). Insofar as the association of FV-Leiden with coronary artery disease (CAD) remains poorly defined, the aim of this study was to determine the prevalence of FV-Leiden in a sample of 68 VTE patients, 69 CAD patients, and 192 randomly selected healthy subjects.

METHODS: Total genomic DNA was extracted from the peripheral blood of study subjects and was used for PCR analysis. The presence (or absence) of FV-Leiden was assessed by PCR using primers flanking the mutant site (nt 1691), followed by hybridization with wild-type ('G') and mutant ('A') biotinylated DNA probes; detection was by DNA enzyme immunoassay (DEIA).

RESULTS: While the prevalence of FV-Leiden in CAD patients was not statistically different from that of healthy subjects (14.5 % vs. 15.1 %; P=0.890, odds ratio 0.95; 95 % confidence interval 0.43--2.06), a significant increase in FV-Leiden prevalence was seen in VTE patients (70.6 % in VTE patients; P<0.001, odds ratio 13.4, 95 % confidence interval 6.9--25.8). Of the 48 VTE patients who tested positive for FV-Leiden, 42 were heterozygotes (G/A), while 6 were homozygotes (A/A) (allele frequency 0.397). All 10 CAD patients positive for FV-Leiden were heterozygote carriers (allele frequency 0.072). While gender was not a factor in FV-Leiden expression, higher prevalence in FV-Leiden was seen in younger (< or =45 years) VTE patients (38/51 vs. 10/17).

CONCLUSION: FV-Leiden is a major inherited risk factor for VTE, with a peak incidence in younger patients, but does not appear to play any role in CAD pathogenesis in the population studied.