Factor VII coagulant activity, factor VII -670A/C and -402G/A polymorphisms, and risk of venous thromboembolism.

ABSTRACT

BACKGROUND: Most epidemiological studies have found no association between levels of factor (F) VIIC and venous thromboembolism (VTE). Our Longitudinal Investigation of Thromboembolism Etiology (LITE) had, in contrast, reported an independent, increased risk of VTE after 7.8 years of follow-up for those with high baseline levels of FVIIC. OBJECTIVE: To confirm whether FVIIC is associated with VTE after 12.6 years of follow-up and to examine whether two FVII gene polymorphisms (-670A/C and -402G/A) are related to VTE occurrence. METHODS: In 19 091 LITE participants with no prior history of VTE or cancer, we measured FVIIC at baseline and identified 404 new VTEs. We also performed a nested case-control study to relate the polymorphisms to VTE (n = 490 without exclusion for cancer or prior VTE). RESULTS: FVIIC was not independently associated with VTE occurrence after extended follow-up. Multivariable-adjusted rate ratios for VTE were 1.00, 1.00, 0.94, 1.00, and 1.38 (P-trend = 0.48) for the <25th, 25th-49th, 50th-74th, 75th-94th, and >or=95th percentiles of FVIIC, respectively. The -670C and -402A alleles were in high linkage disequilibrium, and both were associated with greater FVIIC levels. However, neither polymorphism was associated with VTE occurrence. CONCLUSION: After extended follow-up, LITE offers little evidence that a greater FVII level is a risk factor for VTE.