Background High plasma levels of coagulation factor VII havebeen suggested to be predictors of death due to coronary arterydisease. Since polymorphisms in the factor VII gene contributeto variations in factor VII levels, such polymorphisms may beassociated with the risk of myocardial infarction, which isprecipitated by thrombosis.
Methods We studied a total of 444 patients, 311 of whom hadsevere, angiographically documented coronary atherosclerosis.Of these 311 patients, 175 had documentation of a previous myocardialinfarction. As a control group, 133 patients with normal coronaryarteriograms were also included. We measured the levels of activatedfactor VII and assessed three polymorphisms in the factor VIIgene, one involving the promoter (A1 and A2 alleles), one involvingthe catalytic region (R353Q), and one involving intron 7.
Results Each of the polymorphisms influenced factor VII levels.Patients with the A2A2 and QQ genotypes had the lowest levelsof activated factor VII (66 percent and 72 percent lower, respectively,than the levels in patients with the wild-type genotypes). Thefrequencies of the various genotypes in the patients free ofcoronary artery disease were similar to those in the entirepopulation of patients with coronary artery disease. In thelatter group, there were significantly more heterozygotes andhomozygotes for the A2 and Q alleles among those who had nothad a myocardial infarction than among those who had had aninfarction (P=0.008 for the presence of the promoter polymorphismand P=0.01 for the presence of the R353Q polymorphism by chi-squareanalysis). The adjusted odds ratio for myocardial infarctionamong the patients with the A1A2 or RQ genotype was 0.47 (95percent confidence interval, 0.27 to 0.81).
Conclusions Our findings suggest that certain factor VII genotypeshave a role in protection against myocardial infarction. Thismay explain why some patients do not have myocardial infarctiondespite the presence of severe coronary atherosclerosis.
Source Information
From the Department of Clinical and Experimental Medicine (D.G., C.R., O.O., S.F., R.C.) and the Institutes of Clinical Chemistry (F.M.) and Cardiovascular Surgery (A.M.), University of Verona, Verona; and the Department of Biochemistry and Molecular Biology, University of Ferrara, Ferrara (P.F., M.P., F.B.) — both in Italy.
Address reprint requests to Dr. Girelli at the Department of Clinical and Experimental Medicine, University of Verona, Policlinico G.B. Rossi, 37134 Verona, Italy, or at digigi{at}borgoroma.univr.it.
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