Cardiologie clinique et expérimentale
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Bß-Fibrinogen Gene Promoter –455 G/A Polymorphism Associates with Severity of Coronary Artery Stenosis in Male Victims of Sudden Pre-Hospital Death

Martiskainen, Mikkelsson, Goebeler S, Ilveskoski E and Karhunen PJ

Background and Purpose: Elevated fibrinogen levels are associated with the risk of atherosclerotic disease and affected by smoking. In haplotype analyses, the A-allele of the -455 G/A promoter polymorphism of the Bβ-fibrinogen gene (FGB) was most strongly associated with elevated fibrinogen levels. The association of the FGB –455 G/A polymorphism with coronary artery disease (CAD) and its complications have not been studied at the vessel-wall level.

Methods: We measured coronary stenosis as well as coronary and aortic atherosclerotic areas in a prospective autopsy series of 300 middle-aged (33-69 years) men (the Helsinki Sudden Death Study). FGB -455 G/A genotype was determined by PCR.

Results: Genotype distributions were 69.9%, 24.9%, and 5.2% for GG, GA and AA, respectively. In a logistic regression model with age, hypertension, diabetes, body mass index (BMI) and smoking as confounders, there was a significant association between the A-allele of FGB -455 G/A and >50.0% stenosis in coronary arteries (44.0% vs. 25.3 %, OR=2.37, 95% CI 1.25 − 4.48, p=0.008), compared to GG homozygotes. There was no significant genotype- by-smoking interaction on the severity of coronary artery stenosis although the FGB -455 G/A A-allele had a more pronounced effect on stenosis severity. The FGB -455 G/A genotype was not linked with the extent of coronary or aortic atherosclerosis or with myocardial infarction (MI).

Conclusion: Carriers of the A-allele of the FGB –455 G/A polymorphism had more severe coronary artery stenosis but this genotype did not affect the extent of coronary or aortic atherosclerotic lesion areas.