Role of bcii polymorphism of β-chain fibrinogen gene in the risk of familial myocardial infarction (AMI)

High plasma fibrinogen levels are considered a major risk factor for arterial thrombotic diseases. Whether fibrinogen genotype is associated with different levels of fibrinogen or with arterial thrombosis has not been well established so far. We focussed our study on the Bell polymorphism in the -chain of the fibrinogen gene: the polymerase chain reaction was followed by the use of the Bell restriction enzyme to detect alleles B1 and B2. Genotype analyses were performed on one hundred AMI patients who had a familial tendency to arterial thrombosis (with at least one first degree relative suffering of AMI or stroke before 65 years) and one hundred eighty controls (matched for sex, age and regional area), aged 42-74, recruited all over Italy. There was a high difference in allele frequency between cases and controls: the B1 and B2 allele frequencies were respectively 0.82 and 0.18 in controls, and 0.71 and 0.29 in AMI patients (*p<0.0001). Genotype distributions were 45 and 123 B1B1 subjects vs 54 and 57 (B1B2+B2B2) subjects, respectively in AMI vs controls (*p<0.0001). We evaluated also the effect of the Bell genotype on fibrinogen levels in AMI patients: the mean levels in B1B1 and (B1B2+B2B2)-subjects were significantly different: 276±52 vs 336±80 mg/L (*p<0.001). No correlation was found between plasma fibrinogen levels and age, cholesterol, apoB, LDL and HDL levels both in patients carrying the B1B1 and the (B1B2+B2B2) genotype. In the stepwise regression analysis the (B1B2+B2B2)-genotype, age and sex accounted respectively for 16, 7 and 4% of the variance in fibrinogen levels in AMI patients. These data provide strong evidence for a role of the B2 allele in increasing the risk of familial AMI and add new evidence for a genetic control of fibrinogen levels.