A VARIANT OF BETA-FIBRINOGEN IS A GENETIC RISK FACTOR FOR CORONARY-ARTERY DISEASE AND MYOCARDIAL-INFARCTION

Background: Coronary artery disease is a complex trait caused by a num ber of genetic and environmental factors. Genes involved in hemostasis and coagulation are excellent candidate genes for CAD and its thrombo tic complications, ie, myocardial infarction (MI) and unstable angina. Methods: We determined the frequency of beta-fibrinogen genotypes in a homogenous patient population with CAD undergoing coronary angioplas ty and in a comparable group in the general population. DNA was extrac ted from the blood and genotypes were determined by polymerase chain r eaction, restriction mapping with Hha-1 and gel electrophoresis. Cases and controls were also genotyped for a G(17382)T polymorphism in the (beta-Myosin heavy chain) (beta-MyHC) gene, which is not a candidate g ene for CAD. Results: The distribution of beta-MyHC G/T genotypes and the frequency of alleles were similar in cases and controls. However, the beta-fibrinogen G/G genotype was present in 71% of patients with C AD as compared to 54% in the general population (p = 0.0001, OR: 2.1, 95% CI: 1.7-2.8). Seventy-one percent of patients with MI and 72% of p atients with unstable angina had G/G genotype (p = 0.003, OR: 2.0, 95% CI: 1.3-3.3, and p = 0.005, OR: 2.1, 95% CI: 1.3-3.7, respectively). Sixty-nine percent of male and 82% of female patients with CAD had the G/G genotype as compared to 56% and 530/0 in the general population, respectively (p = 0.0381, and 0.0003, respectively). Multivariate regr ession analysis showed that the allele G was an independent predictor of case-control status or risk of MI in a codominant manner (F = 86.8, p<0.0001). Conclusions: beta-fibrinogen G/G genotype is a genetic risk factor for predisposition to CAD and its thrombotic complications.