BCL-I POLYMORPHISM IN THE FIBRINOGEN BETA-CHAIN GENE IS ASSOCIATED WITH THE RISK OF FAMILIAL MYOCARDIAL-INFARCTION BY INCREASING PLASMA-FIBRINOGEN LEVELS - A CASE-CONTROL STUDY IN A SAMPLE OF GISSI-2 PATIENTS

The aim of this study was to investigate the association of the Bcl I beta-chain fibrinogen polymorphism with the risk of acute myocardial i nfarction (AMI) and its relationship with fibrinogen levels in the Ita lian population. We studied 102 AMI patients, selected within the fram ework of the GISSI-2 trial, who had a familial history of arterial thr ombosis (at least one first-degree relative suffering from AMI or stro ke before 65 years) and 173 control subjects (with neither AMI nor per sonal or familial history of arterial thrombosis). All subjects were I talian. Patients showed Fibrinogen levels higher than control subjects . There was a highly significant difference in allele frequency in cas es versus control subjects, the B2 allele frequencies being respective ly 0.28 versus 0.17 (P=.002). In multivariate analysis, adjusted for s ex, age, smoking habits, and history of hyperlipidemia, hypertension, or diabetes, the (B1B2+B2B2) genotype was associated with a higher ris k of AMI (odds ratio 2.4, 95% confidence interval, 1.2 to 4.6). The Bc l I genotype was also associated with fibrinogen levels, independently of gender and smoking habits, the (B1B2+B2B2) subjects showing the hi ghest levels in both cases and control subjects. The difference in fib rinogen levels between cases and control subjects was significantly in fluenced by the genotype (significant interaction, P=.042) The B2 alle le of the Bcl I polymorphism in the beta-chain of the fibrinogen gene is a new factor associated with the risk of familial AMI through its a ssociation with fibrinogen levels. These data provide evidence for a c ausal role of fibrinogen in familial AMI.