A Variant of β Fibrinogen is a Genetic Risk Factor for Coronary Artery Disease and Myocardial Infarction

Background Coronary artery disease is a complex trait caused by a number of genetic and environmental factors. Genes involved in hemostasis and coagulation are excellent candidate genes for CAD and its thrombotic complications, ie, myocardial infarction (MI) and unstable angina. Methods We determined the frequency of β-fibrinogen genotypes in a homogenous patient population with CAD undergoing coronary angioplasty and in a comparable group in the general population. DNA was extracted from the blood and genotypes were determined by polymerase chain reaction, restriction mapping with Hha -1 and gel electrophoresis. Cases and controls were also genotyped for a G 17382 T polymorphism in the (B-Myosin heavy chain) (β-MyHC) gene, which is not a candidate gene for CAD. Results The distribution of B-MyHC G/T genotypes and the frequency of alleles were similar in cases and controls. However, the β-fibrinogen G/G genotype was present in 71% of patients with CAD 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 patients 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 53% in the general population, respectively (p = 0.0381, and 0.0003, respectively). Multivariate regression 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 β-fibrinogen G/G genotype is a genetic risk factor for predisposition to CAD and its thrombotic complications.