Contribution of the -455G/A Polymorphism at the β-fibrinogen Gene to Erythrocyte Aggregation in Patients with Coronary Artery Disease

Xiaoduan Weng; Guy Cloutier; Jacques Genest Jr.

doi:10.1055/s-0037-1614845

Thrombosis and Haemostasis, Inhaltsverzeichnis

Thromb Haemost 1999; 82(05): 1406-1411
DOI: 10.1055/s-0037-1614845

Rapid Communications

Schattauer GmbH

Contribution of the -455G/A Polymorphism at the β-fibrinogen Gene to Erythrocyte Aggregation in Patients with Coronary Artery Disease

Xiaoduan Weng

¹From Laboratory of Biomedical Engineering, Clinical Research Institute of Montréal, Québec, Canada

,

Guy Cloutier

¹From Laboratory of Biomedical Engineering, Clinical Research Institute of Montréal, Québec, Canada

³Department of Medicine, Faculty of Medicine, University of Montréal, Canada

,

Jacques Genest Jr.

²Laboratory of Cardiovascular Genetics, Clinical Research Institute of Montréal, Québec, Canada

³Department of Medicine, Faculty of Medicine, University of Montréal, Canada

› Institutsangaben

Abstract

Summary

Background. A high level of red blood cell (RBC) aggregation has been consistently found in patients with coronary artery disease (CAD) in case-control studies. Plasma fibrinogen has been shown to promote RBC aggregability. The purpose of this study was to investigate the influence of the genetic variability of the β-fibrinogen gene on RBC aggregation in patients with CAD. Methods and Results. The genotype of the β-fibrinogen gene locus was determined by polymerase chain reaction using the restriction enzyme HaeIII for a G to A substitution at position -455 upstream from the transcriptional start site in 135 French Canadians with premature CAD (age: 51 ± 7 years). Indices measuring the RBC aggregation kinetics (S₁₀) and shear resistance of the aggregates (γS) were obtained by laser reflectometry. Patients were separated into groups by using the medians of S₁₀ and γS. Using χ² analyses, the distribution of the -455GG, -455GA, and -455AA genotypes in the groups with high levels of S₁₀ (0.43, 0.49, and 0.08) and γS (0.45, 0.49, and 0.06) were found to be significantly distinct from those in the groups with low levels of S₁₀ (0.67, 0.27, and 0.06; p <0.05) and γS (0.70, 0.23, and 0.07; p <0.01). High levels of RBC aggregation were closely associated with the rare -455A allele. Multivariate linear regression analyses showed that S₁₀ was positively correlated with the linear combination of the fibrinogen concentration, age, and the -455G/A genotype (adjusted r = 0.63, p <0.0001). Fibrinogen and age were positive determinants, and HDL-cholesterol was a negative predictor of γS (adjusted r = 0.51, p <0.0001). Conclusion. These findings support the hypothesis that RBC hyperaggregation in premature CAD may be associated with the β-fibrinogen -455G/A polymorphism. This association may be explained by a change in the concentration and/or the functional properties of the fibrinogen protein.

Keywords

Erythrocyte aggregation - β-fibrinogen gene - genetics - coronary artery disease - fibrinogen - lipids - lipoproteins

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References
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