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DOI: 10.1055/s-0028-1103367
Genetic Architecture of Tissue-Type Plasminogen Activator and Plasminogen Activator Inhibitor-1
Publikationsverlauf
Publikationsdatum:
28. November 2008 (online)
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ABSTRACT
Important biochemical constituents of the fibrinolytic system include tissue-type plasminogen activator (t-PA) and plasminogen activator inhibitor-1 (PAI-1). In the current review, we aim to describe the genetic architecture of t-PA and PAI-1. Several genetic polymorphisms in the t-PA and PAI-1 gene have been found to be associated with t-PA and PAI-1 levels in different patient cohorts. However, these genetic variations explain only a minor part of the heritability of t-PA and PAI-1, suggesting that genes in other pathways may influence t-PA and PAI-1 levels, and that epistasis and gene-environment interactions may play an important role in determining plasma levels of t-PA and PAI-1. Several studies reported that interindividual variation in plasma levels of t-PA and PAI-1 are significantly influenced by common polymorphisms in genes from the renin-angiotensin and bradykinin systems. In addition, we and others documented several gene-environment interactions and epistatic effects of genetic polymorphisms in the renin-angiotensin, bradykinin, and fibrinolytic systems on plasma t-PA and PAI-1 levels. In future studies, we need to consider high-order interactions and additional polymorphisms in genes from other (unknown) pathways detected by genome-wide association studies to fully understand the complex genetic architecture of these important intermediate quantitative traits and thereby thrombosis.
KEYWORDS
PAI-1 - t-PA - plasminogen - gene - polymorphism - genetic architecture
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Dr. Folkert W Asselbergs
Department of Cardiology, University Medical Center Groningen, University of Groningen
P.O. Box 30001, Hanzeplein 1, 9700 RB, Groningen, The Netherlands
eMail: fwasselbergs@hotmail.com