Mutation in the promoter region of the beta-fibrinogen gene and the risk of future myocardial infarction, stroke and venous thrombosis.

Abstract

Polymorphisms in the promoter region of the beta-fibrinogen gene are associated with increased plasma fibrinogen levels. We investigated whether the distribution of the C148T polymorphism is associated with an increase in cardiovascular risk. In a nested case-control design, the distribution of the C148T polymorphism was investigated among 751 participants in the Physicians' Health Study who subsequently developed myocardial infarction, stroke or venous thromboembolism (cases) and among 751 age- and smoking-matched controls over follow-up of 8.6 years. Frequency of the T allele was similar among men who had myocardial infarction (22.7%, P=0.5), stroke (18.4%, P=0.2) or venous thromboembolism (17.0%, P=0.1) compared with those with no cardiovascular events (21.5%). The relative risk for any vascular event among men homozygous or heterozygous for the T allele compared with men homozygous for the C allele was 0.94 (95% CI 0.76-1.16). We found no evidence of an association between the T allele and myocardial infarction (relative risk 1.06; 95% CI 0.82-1.36), stroke (0.87, 0.63-1.21) or venous thromboembolism (0.75; 0.51-1.08). Analysis adjusted for aspirin use and traditional cardiovascular risk factors had no significant effect on these findings. In a large prospective cohort, carriage of the T allele for the C148T mutation in the beta-fibrinogen promoter gene was not associated with an increased subsequent risk of cardiovascular events.