Association of a Common Polymorphism in the Factor XIII Gene with Myocardial Infarction

Hans P. Kohler; Max H. Stickland; Nicholas Ossei-Gerning; Angela Carter; Hanna Mikkola; Peter J. Grant

doi:10.1055/s-0037-1614250

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 1998; 79(01): 8-13
DOI: 10.1055/s-0037-1614250

Review Article

Schattauer GmbH

Association of a Common Polymorphism in the Factor XIII Gene with Myocardial Infarction

Hans P. Kohler

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

,

Max H. Stickland

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

,

Nicholas Ossei-Gerning

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

,

Angela Carter

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

,

Hanna Mikkola

^*From the Department of Clinical Chemistry, University of Helsinki, Meilathi Hospital, Helsinki, Finland

,

Peter J. Grant

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

› Author Affiliations

Abstract

Summary

Factor XIII when activated by thrombin, crosslinks fibrin, however its role in thrombotic disorders is unknown. A common point mutation (G T) in exon 2 of the A-subunit gene which codes for an amino acid change three amino acids from the thrombin activation site (Factor XIIIVal34Leu) is a candidate for a role in the pathogenesis of acute myocardial infarction. Factor XIII genotype frequencies were determined in a case-control study of 398 caucasian patients and 196 healthy controls. Patients had undergone angiography for investigation of coronary artery disease and were evaluated for a history of myocardial infarction. The prevalence of the mutation was lower in patients with myocardial infarction than without (32% vs. 50%), p = 0.0009 and than in controls (32% vs. 48%), p = 0.005. Patients possessing the mutation with a history of myocardial infarction had higher PAI-1 concentrations (mean, 27.9 vs. 16.7 ng/ml, p = 0.004) and the PAI-1 4G/4G genotype was commoner (43% vs. 26%, p = 0.03). There was no difference in PAI-1 4G/4G genotype (33% vs. 32%) and PAI-1 levels (mean, 21.0 vs. 20.9 ng/ml) in patients possessing wild type with MI compared to those without MI. These results indicate that the G T mutation coding for factor XIIIVal34Leu is protective against myocardial infarction and suggest a mechanism whereby elevated levels of PAI-1 may contribute to vascular risk.

Full Text

References

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