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 number of genetic and environmental factors. Genes involved in hemostasis and coagulation are excellent candidate genes for CAD and its thrombotic complications, i.e., myocardial infarction (MI) and unstable angina.


METHODS
We determined the frequency of beta-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 G17382T polymorphism in the (beta-Myosin heavy chain) (beta-MyHC) gene, which is not a candidate gene 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 CAD as compared to 54% in the general population (p = 0.00001, 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 in 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
beta-fibrinogen G/G genotype is a genetic risk factor for predisposition to CAD and its thrombotic complications.
Yu
Q
Q
Department of Medicine, Baylor College of Medicine, Houston, TX 77030, USA.
Safavi
F
F
Roberts
R
R
Marian
A J
AJ
D000328:Adult; D000368:Aged; D000483:Alleles; D016022:Case-Control Studies; D002894:Chromosomes, Human, Pair 4; D003327:Coronary Disease / Q000097:blood / Q000235:genetics*; D003328:Coronary Thrombosis / Q000097:blood / Q000235:genetics; D005260:Female; D005340:Fibrinogen / Q000235:genetics* / Q000378:metabolism; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000097:blood / Q000235:genetics*; D010446:Peptide Fragments / Q000097:blood / Q000235:genetics*; D012307:Risk Factors
D010446:Peptide Fragments; D005340:Fibrinogen