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Angiotensinogen, angiotensine converting enzyme and plasminogen activator inhibitor-1 gene polymorphism in chronic

Negar Azarpira1, M Bagheri, Gh A Raisjalali

  • 1Organ Transplant Research Center, Nemazi Hospital, Shiraz University of Medical Sciences, Zand street, Shiraz, Iran. negarazarpira@yahoo.com

Molecular Biology Reports
|May 6, 2008
PubMed

Insights

Specific gene variations in angiotensinogen (AGT M235T) and angiotensin-converting enzyme (ACE) are linked to chronic allograft dysfunction (CAD) in kidney transplant recipients. Identifying these genotypes pre-transplant may help predict patients at risk for long-term graft loss.

Area of Science:

  • Nephrology
  • Immunology
  • Genetics

Background:

  • Chronic allograft dysfunction (CAD) is the primary cause of late renal allograft loss, despite improved short-term survival.
  • Current immunotherapies show limited efficacy in preventing or treating CAD.
  • The renin-angiotensin system (RAS) is implicated in chronic kidney disease progression, with plasminogen activator inhibitor-1 (PAI-1) playing a role within the RAS.

Purpose of the Study:

  • To investigate the association between angiotensinogen (AGT M235T), angiotensin-converting enzyme (ACE), and PAI-1 gene polymorphisms and the development of CAD.
  • To identify potential genetic markers for predicting renal transplant dysfunction.

Main Methods:

  • Genotyping for AGT M235T, ACE, and PAI-1 polymorphisms was performed using polymerase chain reaction (PCR) techniques.
  • Polymorphism analysis included sequence-specific primers and restriction fragment length polymorphism (RFLP).
  • The study included 127 renal allograft recipients (77 with CAD, 50 without CAD) and 50 healthy controls.

Main Results:

  • Renal transplant recipients with CAD exhibited significantly higher frequencies of the TT genotype for AGT M235T compared to those without CAD (P < 0.05).
  • Recipients with CAD also showed significantly higher frequencies of the DD genotype for ACE compared to recipients without CAD (P < 0.05).
  • No significant differences in PAI-1 allelic or genotypic distributions were found between groups.

Conclusions:

  • AGT M235T and ACE genotypes are associated with an increased risk of developing chronic allograft dysfunction after kidney transplantation.
  • Pre-transplant determination of AGT M235T and ACE genotypes may aid in identifying patients susceptible to long-term renal transplant dysfunction.
  • PAI-1 polymorphisms did not show a significant association with CAD in this cohort.

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