title: Contribution of the -455G/A polymorphism at the beta-fibrinogen gene to erythrocyte aggregation in patients with coronary artery disease.
abstract: 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 beta-fibrinogen gene on RBC aggregation in patients with CAD.
  
  
  RESULTS
  The genotype of the beta-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 (gammaS) were obtained by laser reflectometry. Patients were separated into groups by using the medians of S10 and gammaS. Using chi2 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 gammaS (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 gammaS (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 gammaS (adjusted r = 0.51, p<0.0001).
  
  
  CONCLUSIONS
  These findings support the hypothesis that RBC hyperaggregation in premature CAD may be associated with the beta-fibrinogen -455G/A polymorphism. This association may be explained by a change in the concentration and/or the functional properties of the fibrinogen protein.
authors.affiliation: Laboratory of Biomedical Engineering, Clinical Research Institute of Montréal, Québec, Canada.
authors.forename: X
authors.initials: X
authors.lastname: Weng
authors.forename: G
authors.initials: G
authors.lastname: Cloutier
authors.forename: J
authors.initials: J
authors.lastname: Genest
mesh_terms: D020121:5' Untranslated Regions / Q000235:genetics*; D000328:Adult; D015897:Comorbidity; D003327:Coronary Disease / Q000097:blood / Q000453:epidemiology / Q000235:genetics*; D004903:Erythrocyte Aggregation; D005260:Female; D005340:Fibrinogen / Q000235:genetics*; D005786:Gene Expression Regulation / Q000235:genetics; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012150:Polymorphism, Restriction Fragment Length; D011792:Quebec; D012907:Smoking / Q000097:blood
chemical_list: D020121:5' Untranslated Regions; D005819:Genetic Markers; D005340:Fibrinogen