Genetic and environmental influences on the fibrinolytic system: a twin study

Dirk Peetz; Anja Victor; Petra Adams; Hilde Erbes; Gerd Hafner; Karl J. Lackner; Thomas Hoehler

doi:10.1160/TH04-01-0001

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2004; 92(02): 344-351
DOI: 10.1160/TH04-01-0001

Blood Coagulation, Fibrinolysis and Cellular Haemostasis

Schattauer GmbH

Genetic and environmental influences on the fibrinolytic system: a twin study

Authors

Dirk Peetz

¹Institute of Clinical Chemistry and Laboratory Medicine, Mainz, Germany
Anja Victor

²Institute of Medical Biometry, Epidemiology and Informatics, Mainz, Germany
Petra Adams

³Department of Internal Medicine, Johannes Gutenberg-University, Mainz, Germany
Hilde Erbes

¹Institute of Clinical Chemistry and Laboratory Medicine, Mainz, Germany
Gerd Hafner

⁴Elisabeth-Hospital, Essen, Germany
Karl J. Lackner

¹Institute of Clinical Chemistry and Laboratory Medicine, Mainz, Germany
Thomas Hoehler

³Department of Internal Medicine, Johannes Gutenberg-University, Mainz, Germany

Abstract

Summary

The determination of heritability is a key issue to assess the predictive power of polymorphisms for disease in clinical studies. The aim of this study was to determine the heritability of proteins and activation markers of the fibrinolytic system in a large cohort of healthy twins. Heritability was calculated as 0.76 for thrombin activatable fibrinolysis inhibitor (TAFI), 0.44 for plasminogen activator inhibitor-1 (PAI-1), and 0.43 for tissue plasminogen activator. No significant genetic influence was observed for α₂-antiplasmin-plasmin-complex and D-dimer. Heritability explained by single gene polymorphisms was 25.2% for TAFI 505G>A, 31.5% for 1542C>G, and 50.0% for combination of both. The influence on TAFI levels of 1542C>G (CC→GG, median: −280.5%) was considerably stronger than that of 505G>A (GG→AA, median: +49.3%) and in both cases there seems to be a dose-response relationship. Significant environmental influences on TAFI levels were observed for combined interaction terms (age*sex and bmi*sex). The PAI-1 4G/5G polymorphism explained 56.4% of the calculated heritability. The genetic variables accounting for the 43% heritability of tPA remain unknown. Our data show that the production of several key components of the fibrinolytic system is strongly genetically determined. This genetic influence is accounted for in large part but not completely by a limited number of polymorphisms within the respective genes associated with plasma levels of the gene products.

Keywords

Fibrinolysis inhibitors - thrombin activatable fibrinolysis inhibitor (TAFI) / carboxypeptidases - gene mutations - plasminogen activators

Full Text

References

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