Variation of the factor VII gene and ischemic heart disease in Japanese subjects

BACKGROUND: Polymorphisms of the 5' region (5'FT), an intronic mutation (IVS7), and the 353Arg-Gln (R353Q) substitution of the factor VII gene have been reported to be associated with the plasma level of factor VII. Greater than normal levels of factor VII have also been reported to be associated with atherothrombotic events. However, the significance of factor VII gene polymorphism in the pathogenesis of ischemic heart diseases (IHD) has not been confirmed. OBJECTIVE: To determine whether these three factor VII gene polymorphisms are associated with levels of factor VII in Japanese subjects, and whether these three polymorphisms of the factor VII gene are associated with the risk of myocardial infarction. METHODS: We studied three polymorphisms of the factor VII gene, 5'FT, IVS7, and R353Q polymorphisms, for 493 Japanese subjects consisting of 285 subjects without clinical evidence of ischemic heart disease (non-IHD group) and 208 myocardial infarction patients (myocardial infarction group). We also assessed the plasma levels of factor VII antigen (FVIIag) in 103 subjects in the non-IHD group. RESULTS: Multiple regression analysis revealed that the level of FVIIag was significantly associated with age, body mass index, cholesterol level and a polymorphism of the factor VII gene (5'FT). Logistic analysis of 493 subjects revealed that cholesterol level [P = 0.0036, odds ratio 1.010, 95% confidence interval (CI) 1.003-1.017], smoking (P = 0.0001, odds ratio 5.522, (95% CI 2.684-11.364) and diabetes mellitus (P = 0.0001, odds ratio 6.450, (95% CI 2.953-14.088) were risk factors for myocardial infarction. However, the three polymorphisms of factor VII gene were not associated with risk of myocardial infarction. CONCLUSION: The polymorphisms of the factor VII gene influenced the levels of factor VII but were not significantly associated with risk of myocardial infarction in Japanese subjects.