Tissue-type Plasminogen Activator –7,351C/T Enhancer Polymorphism Is Associated with a First Myocardial Infarction

Per Ladenvall; Lars Johansson; Jan-Håkan Jansson; Sverker Jern; Torbjörn K. Nilsson; Anna Tjärnlund; Christina Jern; Kurt Boman

doi:10.1055/s-0037-1612951

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2002; 87(01): 105-109
DOI: 10.1055/s-0037-1612951

Review Article

Schattauer GmbH

Tissue-type Plasminogen Activator –7,351C/T Enhancer Polymorphism Is Associated with a First Myocardial Infarction

Per Ladenvall^*

¹Cardiovascular Institute, Clinical Experimental Research Laboratory, Sahlgrenska University Hospital/Östra, Göteborg University, Göteborg

,

Lars Johansson^*

²Department of Medicine-Geriatric, Skellefteå County Hospital, Department of Public Health and Clinical Medicine, Umeå University, Umeå

,

Jan-Håkan Jansson

²Department of Medicine-Geriatric, Skellefteå County Hospital, Department of Public Health and Clinical Medicine, Umeå University, Umeå

³The Medical Biobank, Umeå University, Umeå

,

Sverker Jern

¹Cardiovascular Institute, Clinical Experimental Research Laboratory, Sahlgrenska University Hospital/Östra, Göteborg University, Göteborg

,

Torbjörn K. Nilsson

⁴Department of Clinical Chemistry, Umeå University Hospital, Umeå University, Umeå, Sweden

,

Anna Tjärnlund

¹Cardiovascular Institute, Clinical Experimental Research Laboratory, Sahlgrenska University Hospital/Östra, Göteborg University, Göteborg

,

Christina Jern

¹Cardiovascular Institute, Clinical Experimental Research Laboratory, Sahlgrenska University Hospital/Östra, Göteborg University, Göteborg

,

Kurt Boman

²Department of Medicine-Geriatric, Skellefteå County Hospital, Department of Public Health and Clinical Medicine, Umeå University, Umeå

³The Medical Biobank, Umeå University, Umeå

› Author Affiliations

Abstract

Summary

We recently identified a polymorphic Sp1 binding site in an enhancer at the tissue-type plasminogen activator (tPA) locus (tPA –7,351C/T), which was associated with vascular tPA release. Subjects homozygous for the –7,351C allele had twice the tPA release rate compared to subjects carrying the –7,351T allele. In this study we tested the hypothesis that the tPA –7,351C/T polymorphism is associated with myocardial infarction (MI). In a population-based prospective nested case-control study within northern Sweden, genotypes were determined among 61 MI cases and 120 controls. In a multivariate model, the tPA –7,351C/T polymorphism (OR 2.68 for T allele carriers; 95% CI 1.31– 5.50), tPA antigen (OR 1.16; 95% CI 1.07–1.25) and apo A-I (OR, 0.997; 95% CI 0.995–0.999) were independently associated with a first MI. These findings suggest that genetic markers of local tPA release and circulating steady-state tPA levels carry independent prognostic information.

Keywords

Myocardial infarction - tissue-type plasminogen activator - enhancer - polymorphism

Full Text

References

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