FXII (46C→T) Polymorphism and In Vivo Generation of FXII Activity

H. P. Kohler; T. S. Futers; P. J. Grant

doi:10.1055/s-0037-1614565

Thrombosis and Haemostasis, Inhaltsverzeichnis

Thromb Haemost 1999; 81(05): 745-747
DOI: 10.1055/s-0037-1614565

Rapid Communication

Schattauer GmbH

FXII (46C→T) Polymorphism and In Vivo Generation of FXII Activity

Gene Frequencies and Relationship in Patients with Coronary Artery Disease

H. P. Kohler

¹From the Unit of Molecular Vascular Medicine, Leeds General Infirmary, University of Leeds, UK

,

T. S. Futers

¹From the Unit of Molecular Vascular Medicine, Leeds General Infirmary, University of Leeds, UK

,

P. J. Grant

¹From the Unit of Molecular Vascular Medicine, Leeds General Infirmary, University of Leeds, UK

› Institutsangaben

Abstract

Summary

Increased Factor XIIa concentrations have been found in association with coronary artery disease. Recently, a common 46 C to T point mutation in exon 1 of the factor XII gene has been described which is associated with lower FXII clotting activity and lower zymogen levels in relation to possession of the T allele. It is not known whether this polymorphism relates to the phenotypes of FXIIa in vivo or to coronary artery disease. The aim of the study was to investigate the interaction of this polymorphism with FXIIa plasma levels and to study the prevalence of the polymorphism in 266 patients with suspected coronary artery disease characterised by angiography and in 185 healthy controls. FXIIa levels were strongly associated with FXII genotype with lower levels with increasing numbers of T alleles (p <0.0001). There was no difference between the prevalence of this polymorphism in patients with MI compared to those without MI and controls and between all patients and controls (p ≥0.2, chi-square test). There was no association between extent of coronary artery disease (0, 1, 2, and 3 vessel disease) and FXII genotype. In conclusion, the common 46 C to T point mutation is strongly associated with FXIIa but the present study did not show an association with coronary artery disease. The role of this polymorphism in other thrombotic disorders such as ischemic stroke and venous thrombosis and its clinical significance in FXII deficient states remains to be investigated.

Volltext

Referenzen

References
1 Revak SD, Cochrane CG, Johnston AR, Hugli TE. Structural changes accompanying enzymatic activation of human Hageman factor.. J Clin Invest 1974; 54: 619-27.
2 Revak SD, Cochrane CG. The relationship of structure and function in human Hageman factor. The association of enzymatic and binding activities with separate regions of the molecule.. J Clin Invest 1976; 57: 852-60.
3 Revak SD, Cochrane CG, Bouma BN, Griffin JH. Surface and fluid phase activities of two forms of activated Hageman factor produced during contact activation of plasma.. J Experimental Medicine 1978; 147: 719-29.
4 Kanaji T, Okamura T, Osaki K, Kuroiwa M, Shimoda K, Hamasaki N, Niho Y. A common genetic polymorphism (46 C to T substitution) in the 5’-untranslated region of the coagulation factor XII gene is associated with low translation efficiency and decrease in plasma factor XII level.. Blood 1998; 91: 2010-4.
5 Kohler HP, Carter AM, Stickland MH, Grant PJ. Levels of activated FXII in survivors of myocardial infarction – Association with circulating risk factors and extent of coronary artery disease.. Thromb Haemost 1998; 79: 14-8.
6 Miller GJ, Esnouf MP, Burgess I A, Cooper JA, Mitchell JP. Risk of coronary heart disease and activation of factor XII in middle-aged men.. Arterioscler Thromb Vasc Biol 1997; 17: 2103-6.
7 Kohler HP, Stickland MH, Ossei-Gerning N, Carter AM, Mikkola H, Grant PJ. Association of a common polymorphism in the factor XIII gene with myocardial infarction.. Thromb Haemost 1998; 79: 8-13.
8 Cool DE, MacGillivray RTA. Characterisation of the human blood coagulation factor XII gene. Intron/exon gene organisation and analysis of the 5’-flanking region.. J Biol Chem 1987; 262: 13662-73.
9 Ford RP, Esnouf MP, Burgess I A, Sarphie A. An enzyme-linked immunosorbent assay (ELISA) for the measurement of activated factor XII (Hage-man factor) in human plasma.. J Immunoassay 1996; 17: 119-31.
10 Halbmayer WM, Haushofer A, Schön R, Mannhalter C, Strohmer E, Baumgarten K, Fischer M. The prevalence of moderate and severe FXII (Hage-man factor) deficiency among the normal population: Evaluation of the incidence of FXII deficiency among 300 healthy blood donors.. Thromb Haemost 1994; 71: 68-72.
11 Halbmayer WM, Haushofer A, Radek J, Schön R, Deutsch M, Fischer M. Prevalence of factor XII (Hageman factor) deficiency among 426 patients with coronary heart disease awaiting cardiac surgery.. Coronary Artery Disease 1994; 5: 451-4.