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 ma y be genetically determined, the relation between genetic polymorphism s of factor VII, factor VII blood levels, and the risk of myocardial i nfarction has not been established. Methods We performed a case-contro l study of 165 patients with familiar myocardial infarction (mean [+/- SD] age, 55+/-9 years) and 225 controls without a personal or family h istory of cardiovascular disease (mean age, 56+/-8 years). The polymor phisms involving R353Q and hypervariable region 4 of the factor VI gen e were studied. Factor VII clotting activity and antigen levels were a lso measured. Results Patients with the QQ or H7H7 genotype had a decr eased risk of myocardia[ infarction (odds ratios, 0.08 [95 percent con fidence interval, 0.01 to 0.9] and 0.22 [95 percent confidence interva l, 0.08 to 0.63], respectively). For the R353Q polymorphism, the RR ge notype was associated with the highest risk, followed by the RQ genoty pe and then by the QQ genotype (P<0.001). For the polymorphism involvi ng hypervariable region 4, the combined H7H5 and H6H5 genotypes were a ssociated with the highest risk, followed in descending order by the H 6H6, 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 cl otting 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 fi ndings suggest that certain polymorphisms of the factor VII gene may i nfluence the risk of myocardial infarction. It is possible that this e ffect may be mediated by alterations in factor VII levels. (C) 1998. M assachusetts Medical Society.