Association between TAFI antigen and Ala147Thr polymorphism of the TAFI gene and the angina pectoris incidence

Pierre E. Morange; Irène Juhan-Vague; Pierre Y. Scarabin; Marie C. Alessi; Gérald Luc; Dominique Arveiler; Jean Ferrieres; Philippe Amouyel; Alun Evans; Pierre Ducimetiere; on behalf of the PRIME Study group

doi:10.1055/s-0037-1613387

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2003; 89(03): 554-560
DOI: 10.1055/s-0037-1613387

Vascular Development and Vessel Remodelling

Schattauer GmbH

Association between TAFI antigen and Ala147Thr polymorphism of the TAFI gene and the angina pectoris incidence

The PRIME Study

Authors

Pierre E. Morange

¹Department of Hematology, Hôpital de la Timone, INSERM 99–36 Marseilles, France
Irène Juhan-Vague

¹Department of Hematology, Hôpital de la Timone, INSERM 99–36 Marseilles, France
Pierre Y. Scarabin

²INSERM U258, Villejuif, France
Marie C. Alessi

¹Department of Hematology, Hôpital de la Timone, INSERM 99–36 Marseilles, France
Gérald Luc

³Department of Atherosclerosis, INSERM UR545, Institut Pasteur de Lille, Lille, France
Dominique Arveiler

⁴The Strasbourg MONICA Project, Department of Epidemiology and Public Health, Faculty of Medicine, Strasbourg, France
Jean Ferrieres

⁵The Toulouse MONICA Project, INSERM U588, Department of Epidemiology, Paul Sabatier-Toulouse Purpan University, Toulouse, France
Philippe Amouyel

⁶The Lille MONICA Project, INSERM U508, Institut Pasteur de Lille, France
Alun Evans

⁷The Department of Epidemiology and Public Health, Queen’s University of Belfast, Northern Ireland
Pierre Ducimetiere

²INSERM U258, Villejuif, France

on behalf of the PRIME Study group

Abstract

Summary

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.

Keywords

Angina - arteriosclerosis - coronary disease - fibrinolysis - myocardial infarction

Full Text

References

References
1 Bajzar L, Manuel R, Nesheim ME. Purification and characterization of TAFI, a thrombinactivatable fibrinolysis inhibitor. J Biol Chem 1995; 270: 14477-184.
2 Eaton DL, Malloy BE, Tsai SP. et al Isolation, molecular cloning, and partial characterization of a novel carboxypeptidase B from human plasma. J Biol Chem 1991; 269: 21833-8.
3 Hendriks D, Wang W, Scharpe S. et al Purification and characterization of a new arginine carboxypeptidase in human serum. Biochim Biophys Acta 1990; 1034: 86-92.
4 Redlitz A, Tan AK, Eaton DL. et al Plasma carboxypeptidases as regulators of the plasminogen system. J Clin Invest 1995; 96: 2534-8.
5 Minnema MC, Friederich PW, Levi M. et al Enhancement of rabbit jugular vein thrombolysis by neutralization of factor XI: in vivo evidence for a role of factor XI as an antifibrinolytic factor. J Clin Invest 1998; 101: 10-4.
6 Klement P, Liao P, Bajzar B. A novel approach to arterial thrombolysis. Blood 1999; 94: 2735-43.
7 Refino CJ, DeGuzman L, Schmitt D. et al Consequences of inhibition of plasma carboxypeptidase B on in vivo thrombolysis, thrombosis and haemostasis. Fibrinolysis and Proteolysis 2000; 14: 305-13.
8 Nagashima M, Werner M, Wang M. et al An inhibitor of activated thrombin-activatable fibrinolysis inhibitor potentiates tissue-type plasminogen activator-induced thrombolysis in a rabbit jugular vein thrombolysis model. Thromb Res 2000; 98: 333-42.
9 Chetaille P, Alessi MC, Kouassi D. et al Plasma TAFI antigen variations in healthy subjects. Thromb Haemost 2000; 83: 902-5.
10 Henry M, Aubert H, Morange PE. et al Identification of polymorphisms in the promoter and the 3’ region of the TAFI gene: evidence that plasma antigen levels are strongly genetically controlled. Blood 2001; 97: 2053-8.
11 Zhao L, Morser J, Bajzar L, Nesheim M, Nagashima M. Identification and characterization of two thrombin-activatable fibrinolysis inhibitor isoforms. Thromb Haemost 1998; 80: 949-55.
12 Franco RF, Fagundes MG, Meijers JCM. et al Identification of polymorphisms in the 5’-untranslated region of the TAFI gene: relationship with plasma TAFI levels and risk of venous thrombosis. Haematologica 2001; 86: 510-7.
13 Brouwers GJ, Vos HL, Leebeek FWG. et al A novel, possibly functional, single nucleotide polymorphism in the coding region of the thrombin-activatable fibrinolysis inhibitor (TAFI) gene is also associated with TAFI levels. Blood 2001; 98: 1992-3.
14 Juhan-Vague I, Renucci JF, Grimaux M. et al Thrombin-activatable fibrinolysis inhibitor antigen levels and cardiovascular risk factors. Arterioscler Thromb Vasc Biol 2000; 20: 2156-61.
15 Silveira A, Schatteman K, Goossens F. et al Plasma procarboxypeptidase U in men with symptomatic coronary artery disease. Thromb Haemost 2000; 84: 364-8.
16 Juhan-Vague I, Morange PE, Aubert H. et al Plasma thrombin-activatable fibrinolysis inhibitor (TAFI) antigen concentration and TAFI genotype in relation to myocardial infarction in the north and south of Europe. Arterisocler Thromb Vasc Biol 2002; 22: 867-73.
17 Yarnell JWG. The PRIME study: classical risk factors do not explain the severalfold differences in risk of coronary heart disease between France and Northern Ireland. Q J Med 1998; 91: 667-76.
18 Tunstall-Pedoe H, Kuulasma K, Amouyel P. et al Myocardial infarction and coronary deaths in the World Health Organization MONICA Project. Circulation 1994; 90: 583-612. .
19 Ducimetière P, Ruidavets JB, Montaye M. et al Five-year incidence of angina pectoris and other forms of coronary heart disease in healthy men aged 50-59. in France and Northern Ireland: the prospective Epidemiological Study of Myocardial Infarction (PRIME) Study. Int J Epidemiol 2001; 30: 1057-62.
20 Miller SA, Dykes DD, Polesky HF. A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acid Res 1988; 16: 1215
21 Libby P. Changing concepts of atherogenesis. J Intern Med 2000; 247: 349-58.
22 Swaisgood CM, Schmitt D, Eaton D, Plow EF. In vivo regulation of plasminogen function by plasma carboxypeptidase B. J Clin Invest 2002; 110: 1275-82.
23 Shah PK, Falk E, Badimon JJ. et al Human monocyte-derived macrophages induce collagen breakdown in fibrous caps of athero-sclerotic plaques. Potential role of matrix-degrading metalloproteinases and implications for plaque rupture. Circulation 1995; 92: 1565-9.
24 Fuster V, Fallon JT, Nemerson Y. Coronary thrombosis. Lancet 1996; 348 (Suppl. 01) s7-s10.
25 Campbell W, Okada N, Okada H. Carboxy-peptidase R is an inactivator of complement-derived inflammatory peptides and an inhibitor of fibrinolysis. Immunol Rev 2001; 180: 162-7.