title: Association between TAFI antigen and Ala147Thr polymorphism of the TAFI gene and the angina pectoris incidence. The PRIME Study (Prospective Epidemiological Study of MI).
abstract: Thrombin activatable fibrinolysis inhibitor (TAFI), a recently described inhibitor of fibrinolysis, has been hypothesized as playing a role in atherothrombosis. However, the evidence from retrospective studies, which have evaluated the role of TAFI in vascular risk, is conflicting. In a prospective cohort (the PRIME Study) of nearly 10 000 apparently healthy men recruited in France (Lille, Strasbourg, Toulouse) and Northern Ireland (Belfast), we measured baseline plasma concentration of TAFI antigen among 143 participants (81 from France and 62 from Ireland) who subsequently developed angina pectoris and among 286 age-matched participants who remained free of disease during the 5 years of follow-up. Genotyping of the Ala147Thr polymorphism located in the TAFI gene was performed using an allele specific PCR. In France, mean levels of TAFI were significantly higher at baseline among men who subsequently developed angina pectoris compared with their control subjects (119 versus 107 %; p = 0.02). The risk of future angina pectoris increased with increasing tertiles of TAFI (p = 0.02), such that men in the highest tertile at study entry had a 5-fold higher relative risk than those in the lowest tertile (95% confidence interval, 1.38 to 18.58) after controlling for the conventional cardiovascular risk factors. No such difference was observed in Northern Ireland. In France, Thr/Thr carriers of the Ala147Thr polymorphism were significantly more frequent in cases than in controls (p = 0.01) leading to a relative risk of angina pectoris of 2.7 (95%CI 1.2-5.8). Increase in plasma TAFI antigen levels is a risk factor for angina pectoris in France. Genotyping for the Ala147Thr polymorphism seems to be a reliable tool to assess the risk mediated by TAFI.
authors.affiliation: Department of Hematology, Hôspital de la Timone, INSERM 99-36 Marseilles, France.
authors.forename: Pierre E
authors.initials: PE
authors.lastname: Morange
authors.forename: Irène
authors.initials: I
authors.lastname: Juhan-Vague
authors.forename: Pierre Y
authors.initials: PY
authors.lastname: Scarabin
authors.forename: Marie C
authors.initials: MC
authors.lastname: Alessi
authors.forename: Gérald
authors.initials: G
authors.lastname: Luc
authors.forename: Dominique
authors.initials: D
authors.lastname: Arveiler
authors.forename: Jean
authors.initials: J
authors.lastname: Ferrieres
authors.forename: Philippe
authors.initials: P
authors.lastname: Amouyel
authors.forename: Alun
authors.initials: A
authors.lastname: Evans
authors.forename: Pierre
authors.initials: P
authors.lastname: Ducimetiere
mesh_terms: D019943:Amino Acid Substitution; D000787:Angina Pectoris / Q000201:enzymology* / Q000453:epidemiology / Q000235:genetics*; D000941:Antigens / Q000097:blood; D001483:Base Sequence; D025901:Carboxypeptidase B2 / Q000097:blood* / Q000235:genetics* / Q000276:immunology; D016022:Case-Control Studies; D015331:Cohort Studies; D004247:DNA / Q000235:genetics; D005602:France / Q000453:epidemiology; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009660:Northern Ireland / Q000453:epidemiology; D011110:Polymorphism, Genetic; D011446:Prospective Studies; D012307:Risk Factors
chemical_list: D000941:Antigens; D004247:DNA; D025901:Carboxypeptidase B2