Gene polymorphisms for plasminogen activator inhibitor-1/tissue plasminogen activator and development of allograft

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R L Benza1, H E Grenett, R C Bourge

  • 1Department of Medicine, Division of Cardiovascular Disease, University of Alabama at Birmingham, Alabama, USA. rbenza@cardio.dom.uab.edu

Circulation
|November 24, 1998
PubMed

Insights

Donor PAI-1 2/2 genotype is linked to increased risk of allograft vasculopathy (Tx CAD) after cardiac transplantation. This genetic marker may help predict Tx CAD development in recipients.

Area of Science:

  • Cardiology
  • Transplantation Immunology
  • Genetics

Background:

  • Impaired fibrinolytic activity is associated with allograft vasculopathy (Tx CAD) severity.
  • Fibrinolytic protein gene polymorphisms may contribute to this impairment.

Purpose of the Study:

  • To investigate the association between donor fibrinolytic protein genotypes and Tx CAD.
  • To determine if specific genotypes predict Tx CAD development.

Main Methods:

  • Identified donor plasminogen activator inhibitor-1 (PAI-1) and tissue plasminogen activator (TPA) genotypes using Southern blot analysis in 48 cardiac allograft recipients.
  • Correlated genotypes with the development of Tx CAD.

Main Results:

  • No association found between donor TPA genotypes and Tx CAD.
  • Donor PAI-1 2/2 genotype was associated with significantly lower freedom from CAD at 12 and 24 months (75% and 45%) compared to other genotypes (P=0.03).
  • Recipients with a 2/2 PAI-1 genotyped allograft had longer ischemic times.

Conclusions:

  • The donor 2/2 PAI-1 genotype is a significant risk factor for developing Tx CAD.
  • This genotype can potentially serve as a screening tool for predicting Tx CAD risk.
Abstract

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