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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
1   The Division of Cardiovascular Genetics, Department of Medicine, University College London Medical School, London UK
,
F R Green
1   The Division of Cardiovascular Genetics, Department of Medicine, University College London Medical School, London UK
,
P Y Scarabin
2   The INSERM U258, Hôpital Broussais, Paris, France
,
V Nicaud
2   The INSERM U258, Hôpital Broussais, Paris, France
,
L Bara
3   The Laboratolre de Thrombose Experimentale, Universite Paris VI, France
,
S J Dawson
1   The Division of Cardiovascular Genetics, Department of Medicine, University College London Medical School, London UK
,
S E Humphries
1   The Division of Cardiovascular Genetics, Department of Medicine, University College London Medical School, London UK
,
A Evans
4   The MONICA project, Belfast, UK
,
G Luc
5   The MONICA project, Lille, France
,
J P Cambou
6   The MONICA project, Toulouse, France
,
D Arveiler
7   The MONICA project, Strasbourg, France
,
A M Henney
1   The Division of Cardiovascular Genetics, Department of Medicine, University College London Medical School, London UK
,
F Cambien
8   The SC No7, Banque dADN pour la Recherche Cardiovasculaire, Paris, France
› Author Affiliations
Further Information

Publication History

Received 15 February 1995

Accepted after revision 09 May 1995

Publication Date:
26 July 2018 (online)

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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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