Polymorphism in the coagulation factor VII gene and the risk of myocardial infarction

Background High blood levels of coagulation factor VII are associated with a risk of ischemic vascular disease. Although factor VI levels may be genetically determined, the relation between genetic polymorphisms of factor VII, factor VII blood levels, and the risk of myocardial infarction has not been established. Methods We performed a case-control study of 165 patients with familiar myocardial infarction (mean [+/-SD] age, 55+/-9 years) and 225 controls without a personal or family history of cardiovascular disease (mean age, 56+/-8 years). The polymorphisms involving R353Q and hypervariable region 4 of the factor VI gene were studied. Factor VII clotting activity and antigen levels were also measured. Results Patients with the QQ or H7H7 genotype had a decreased risk of myocardia[ infarction (odds ratios, 0.08 [95 percent confidence interval, 0.01 to 0.9] and 0.22 [95 percent confidence interval, 0.08 to 0.63], respectively). For the R353Q polymorphism, the RR genotype was associated with the highest risk, followed by the RQ genotype and then by the QQ genotype (P<0.001). For the polymorphism involving hypervariable region 4, the combined H7H5 and H6H5 genotypes were associated with the highest risk, followed in descending order by the H6H6, H6H7, and H7H7 genotypes (P<0.001). Patients with the OQ or H7H7 genotype had lower levels of both factor VI[ antigen and factor VII clotting activity than those with the RR or H6H6 genotype. Patients with the fewest level of factor VII clotting activity had a lower risk of myocardial infarction than those with the highest level (odds ratio, 0.13; 95 percent confidence interval, 0.05 to 0.34). Conclusions Our findings suggest that certain polymorphisms of the factor VII gene may influence the risk of myocardial infarction. It is possible that this effect may be mediated by alterations in factor VII levels. (C) 1998. Massachusetts Medical Society.