Polymorphisms 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 VII 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 familial 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 VII 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 myocardial 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 QQ or H7H7 genotype had lower levels of both factor VII antigen and factor VII clotting activity than those with the RR or H6H6 genotype. Patients with the lowest 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.
Iacoviello
L
L
Department of Vascular Medicine and Pharmacology, Istituto di Ricerche Farmacologiche Mario Negri, Santa Maria Imbaro, Italy.
Di Castelnuovo
A
A
De Knijff
P
P
D'Orazio
A
A
Amore
C
C
Arboretti
R
R
Kluft
C
C
Benedetta Donati
M
M
D000704:Analysis of Variance; D001777:Blood Coagulation / Q000235:genetics; D016022:Case-Control Studies; D005167:Factor VII / Q000032:analysis / Q000235:genetics* / Q000502:physiology; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000097:blood / Q000235:genetics*; D016017:Odds Ratio; D011110:Polymorphism, Genetic; D012306:Risk; D013927:Thrombosis / Q000235:genetics
D005167:Factor VII