The 4G/5G Genetic Polymorphism in the Promoter of the Plasminogen Activator Inhibitor-1 (PAI-1) Gene Is Associated with Differences in Plasma PAI-1 Activity but not with Risk of Myocardial Infarction in the ECTIM Study

S Ye; F R Green; P Y Scarabin; V Nicaud; L Bara; S J Dawson; S E Humphries; A Evans; G Luc; J P Cambou; D Arveiler; A M Henney; F Cambien

doi:10.1055/s-0038-1649833

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 1995; 74(03): 837-841
DOI: 10.1055/s-0038-1649833

Original Article

Clinical Studies

Schattauer GmbH Stuttgart

The 4G/5G Genetic Polymorphism in the Promoter of the Plasminogen Activator Inhibitor-1 (PAI-1) Gene Is Associated with Differences in Plasma PAI-1 Activity but not with Risk of Myocardial Infarction in the ECTIM Study

S Ye

¹The Division of Cardiovascular Genetics, Department of Medicine, University College London Medical School, London UK

,

F R Green

¹The Division of Cardiovascular Genetics, Department of Medicine, University College London Medical School, London UK

,

P Y Scarabin

²The INSERM U258, Hôpital Broussais, Paris, France

,

V Nicaud

²The INSERM U258, Hôpital Broussais, Paris, France

,

L Bara

³The Laboratolre de Thrombose Experimentale, Universite Paris VI, France

,

S J Dawson

¹The Division of Cardiovascular Genetics, Department of Medicine, University College London Medical School, London UK

,

S E Humphries

¹The Division of Cardiovascular Genetics, Department of Medicine, University College London Medical School, London UK

,

A Evans

⁴The MONICA project, Belfast, UK

,

G Luc

⁵The MONICA project, Lille, France

,

J P Cambou

⁶The MONICA project, Toulouse, France

,

D Arveiler

⁷The MONICA project, Strasbourg, France

,

A M Henney

¹The Division of Cardiovascular Genetics, Department of Medicine, University College London Medical School, London UK

,

F Cambien

⁸The SC No7, Banque dADN pour la Recherche Cardiovasculaire, Paris, France

› Author Affiliations

Abstract

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Summary

We have investigated the interrelationships of plasma PAI-1 activity, the PAI-1 4G/5G polymorphism and risk of myocardial infarction (MI) in the ECTIM study, a case-control study of MI based in Belfast, Lille, Strasbourg and Toulouse. Mean PAI-1 levels in cases were similar across all centres but in controls, levels in the French centres were significantly higher. Only in Belfast were PAI-1 levels higher in cases (11.7AU/ml) than controls (10.5AU/ml). The PAI-1 4G allele frequency was similar in cases and controls (0.55 and 0.54). In all groups, 4G homozygotes had the highest mean plasma PAI-1 level (4G4G vs 5G5G; cases overall: 14.2 vs 12.1 AU/ml; controls overall: 15.0 vs 12.6AU/ml), with the heterozygotes generally intermediate. The data from Belfast are consistent with the literature implicating PAI-1 level as an MI risk factor. In ECTIM, the PAI-1 4G/5G polymorphism is not a genetic risk factor for MI but is associated with PAI-1 activity. Thus homozygosity for the 4G allele may predispose to elevated PAI-1 and impaired fibrinolysis, perhaps requiring interaction with other genetic or environmental factors to influence MI risk.

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References

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