The decanucleotide insertion/deletion polymorphism in the promoter region of the coagulation factor VII gene and the risk of familial myocardial infarction

Recently, an association has been found between factor VIT polymorphisms an d the risk of familial myocardial infarction. To obtain a thorough evaluati on of the influence of factor VII gene on the risk of myocardial infarction , we extended our analysis to the role of a decanucleotide insertion/deleti on functional polymorphism (-323 0/10-bp) in the promoter region of factor VII and to possible interactions with the HVR4 intron polymorphism. We perf ormed a case-control study of 176 patients with myocardial infarction, over 45 years, who had a familial history of arterial thrombosis and 227 contro l subjects without a personal or family history of cardiovascular disease. The frequency of the rare allele of 10 bp was lower in cases (0.14 95% CI, 0.10-0.17) than in controls (0.19 95% CI, 0.16-0.23; chi(2)=4.7, p=0.03). A llowing for Hardy-Weinberg equilibrium in controls and testing for associat ion under restricted maximisation, there was a significant difference in ge notype frequency between cases and controls (p=0.02). Carriers of the 10-bp allele had an odds ratio for myocardial infarction of 0.65 (95% CI, 0.37-1 .12), in multivariate logistic regression analysis. Combination analysis of -323 0/10-bp and HVR4 polymorphisms shows half reduction in the risk of my ocardial infarction in comparison with the reference group for all the othe r groups, suggesting that there was no additivity between the effect of the 10-bp and the H7 alleles. Our findings suggest that the promoter polymorph ism of factor VII gene may influence the risk of familial myocardial infarc tion, (C) 2000 Elsevier Science Ltd. All rights reserved.