Beta-fibrinogen gene-455 G/A polymorphism and fibrinogen levels. Risk factors for coronary artery disease in subjects with NIDDM.

OBJECTIVE

To investigate the association of a G/A polymorphism at position -455 of the beta-fibrinogen gene and fibrinogen levels in the development of coronary artery disease (CAD) in subjects with NIDDM.

RESEARCH DESIGN AND

METHODS

In 187 Caucasian subjects with NIDDM, presence of CAD was taken as a clinical history of angina, myocardial infarction, coronary angioplasty, or coronary artery bypass grafting, confirmed from medical case notes.

RESULTS

Fibrinogen levels were significantly higher in subjects with CAD (n = 38, 3.41 [3.12-3.73] g/l) than those without (n = 149, 2.99 [2.87-3.11] g/l, P = 0.004 [geometric mean, 95% CI]). Comparing the genotype frequencies by chi 2 testing, there was a significant difference between subjects with CAD (GG = 0.84, GA + AA = 0.16) and those without (GG = 0.64, GA + AA = 0.36, P = 0.02). In a logistic regression model, including age, BMI, cholesterol, sex, smoking, triglycerides, and plasminogen activator inhibitor antigen as covariates, genotype and fibrinogen levels were significantly associated with CAD. The odds ratio for having CAD in individuals homozygous for the G allele compared with those possessing the A allele was 1.77 (1.08-2.90), P = 0.03; and for an increase of 1 g/l in fibrinogen levels was 1.60 (1.00-2.60), P = 0.05.

CONCLUSIONS

These data suggest a relationship between the -455 G/A beta-fibrinogen gene polymorphism and the development of CAD in subjects with NIDDM. This relationship was not associated with variations in fibrinogen levels, suggesting that this polymorphism may be in linkage with a polymorphism within the coding region of the beta-fibrinogen gene, which results in an alteration in the stability of the fibrin clot.