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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2002;22:867.)
© 2002 American Heart Association, Inc.

Thrombosis

Plasma Thrombin-Activatable Fibrinolysis Inhibitor Antigen Concentration and Genotype in Relation to Myocardial Infarction in the North and South of Europe

I. Juhan-Vague; P.E. Morange; H. Aubert; M. Henry; M.F. Aillaud; M.C. Alessi; A. Samnegård; E. Hawe; J. Yudkin; M. Margaglione; G. Di Minno; A. Hamsten; S.E. Humphries on behalf of the HIFMECH Study Group^*

From the Laboratoire d’Hématologie (I.J.-V., P.E.M., H.A., M.H., M.F.A., M.C.A.), CHU Timone, Inserm EPI 99-36, Marseilles, France; the King Gustaf V Research Institute and Departments of Medicine (A.S., A.H.), Danderyd and Karolinska Hospitals, Karolinska Institute, Stockholm, Sweden; the Centre for Cardiovascular Genetics (E.H., S.E.H.), Rayne Institute, Royal Free and University College Medical School, London, England; the Diabetes and Cardiovascular Disease Academic Unit (J.Y.), Archway Campus, Royal Free and University College Medical School, London, England; and the Instituto di Ricovero e Cura a Carattere Scientifico (M.M., G.D.M.), Ospedale Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy.

Correspondence to Prof Irène Juhan-Vague, Laboratoire d’Hématologie-CHU Timone, 13385 Marseilles cedex 5-France. E-mail ijuhan{at}ap-hm.fr

The thrombin-activatable fibrinolysis inhibitor (TAFI) is a recently described inhibitor of fibrinolysis that decreases plasminogen binding to the fibrin surface. The plasma TAFI concentration is almost entirely genetically determined. We investigated whether plasma TAFI levels and polymorphisms located in the TAFI gene could constitute risk markers of myocardial infarction (MI). Plasma TAFI antigen (Ag) levels were assayed by ELISA and 2 TAFI gene polymorphisms (Ala147Thr and C+1542G in the 3' untranslated region) were determined in a large European case-control study. This study compared 598 men recruited 3 to 6 months after MI with 653 age-matched controls from North Europe (Stockholm, Sweden, and London, England) and South Europe (Marseilles, France, and San Giovanni Rotondo, Italy). A TAFI Ag value above the 90th percentile was associated with a significantly lower risk of MI (odds ratio 0.55, P<0.02), indicating that elevated TAFI may be protective against MI. As previously shown, the 2 TAFI gene polymorphisms were in strong linkage disequilibrium and were associated with the TAFI Ag concentration, with carriers of the Thr147 and 1542C alleles having higher levels (P<0.0005). These effects were similar in controls and cases and in each center. There was a difference in allele frequency between cases and controls for the Ala147Thr polymorphism, with Thr147 allele carriers being more frequent in controls than in cases in 2 centers, Stockholm (P=0.03) and San Giovanni Rotondo (P=0.03); the odds ratio for the entire cohort was 0.78 (P<0.05). In conclusion, patients with a recent MI presented lower values of TAFI Ag and higher frequencies of the "TAFI-decreasing" alleles. The geographical differences observed do not contribute to explaining the North-South gradient in MI risk in Europe.

Key Words: thrombin-activatable fibrinolysis inhibitors • myocardial infarction • genetic polymorphisms • fibrinolysis

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