Abstract 5092: Association of Genetic Variation of Factor VII, Interleukin-1 beta, and Interleukin-10 with Risk of Incident Idiopathic Venous Thromboembolism in 22,407 Initially Healthy White Women
While pathways associated with hemostasis and thrombosis are well-documented to influence venous thromboembolism (VTE), whether or not the inflammatory cascade also influences VTE risk remains to be determined. The aim of the present study was to assess the association of 55 inflammation-related, and an additional 22 homeostasis-related candidate gene polymorphisms with risk of incident VTE in a large prospective cohort of initially healthy women. We analyzed data from 22,407 white women who participated in the Women’s Health study. Incident VTE (158 idiopathic, and 180 secondary) during the entire follow-up according to the different genotypes were assessed by Cox proportional-hazards models adjusting for potential risk factors/confounders. False discovery rate (FDR) was used for correction for multiple testing with a 0.20 cut-point. In addition to factor V Leiden (hazard ratio=3.220, 95%CI=1.921–5.396, p<0.0001, q=0.0038), and prothrombin mutation (hazard ratio=2.566, 95%CI=1.637– 4.023, p<0.0001, q=0.0038), factor VII rs6046 (hazard ratio=0.545, 95%CI=0.347– 0.856, p=0.0084, q=0.13), interleukin-1 beta rs1143634 (hazard ratio=0.590, 95%CI=0.436 – 0.800, p=0.0007, q=0.02), and interleukin-10 rs1800872 (hazard ratio=1.418, 95%CI=1.120 –1.796, p=0.0038, q=0.07) were associated with risk of idiopathic VTE. None of the polymorphisms tested were associated with secondary VTE risk. The present investigation replicates our prior report of association of factor VII gene variation with decreased incident idiopathic VTE risk in men, and further suggests that variants in inflammatory pathway may play a role in the pathogenesis of idiopathic VTE.