TY - JOUR
T1 - Genetic architecture of tissue-type plasminogen activator and plasminogen activator inhibitor-1
AU - Asselbergs, Folkert W.
AU - Pattin, Kristine
AU - Snieder, Harold
AU - Hillege, Hans L.
AU - van Gilst, Wiek H.
AU - Moore, Jason H.
PY - 2008/9
Y1 - 2008/9
N2 - 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 reninangiotensin, 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. Copyright © 2008 by Thieme Medical Publishers, Inc.
AB - 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 reninangiotensin, 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. Copyright © 2008 by Thieme Medical Publishers, Inc.
UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=57149096048&origin=inward
UR - https://www.ncbi.nlm.nih.gov/pubmed/19085655
U2 - https://doi.org/10.1055/s-0028-1103367
DO - https://doi.org/10.1055/s-0028-1103367
M3 - Review article
C2 - 19085655
SN - 0094-6176
VL - 34
SP - 562
EP - 568
JO - Seminars in Thrombosis and Hemostasis
JF - Seminars in Thrombosis and Hemostasis
IS - 6
ER -