Angiotensinogen t235 and angiotensin-converting enzyme insertion/deletion polymorphisms associated with the development of posttransplantation diabetes mellitus in renal allograft recipients

Transplant Proc. 2011 Mar;43(2):572-4. doi: 10.1016/j.transproceed.2011.01.046.

Abstract

Background: Genetic polymorphisms of the renin-angiotensin system (RAS) have been reported to play an important role in the pathogenesis of diabetes mellitus and hypertension. In addition, a close association has been reported between RAS and the progression of both diabetes and hypertension. But the role of RAS on the development of posttransplantation diabetes mellitus (PTDM) is not known. For this purpose we investigated the association of polymorphisms in the genes for angiotensin-converting enzyme (ACE) and angiotensinogen (AGT) with the development of PTDM.

Methods: Genotyping for ACE insertion/deletion (I/D) and AGT M235T polymorphisms was performed in 50 patients who underwent renal transplantation during a 5-year period. Group 1 consisted of 23 recipients who developed PTDM and group 2 consisted of 27 recipients that did not have PTDM.

Results: Of 50 patients, 13 (26%) showed the ACE DD, 21 (42%) the ACE ID, and 16 the ACE II genotype. The frequencies of AGT MM, AGT MT, and AGT TT were 0, 54%, and 46%, respectively. Compared with group 2, there were high frequencies of the AGT TT genotype in group 1 recipients (P<.001). In addition the ACE DD genotype was found significantly higher in group 1 patients compared with group 2 patients (P=.001).

Conclusion: The high frequencies of the AGT TT genotype and ACE DD genotype in recipients may contribute to the high prevalence of PTDM. Our data suggest a synergistic effect between the ACE and AGT polymorphism in the risk of PTDM, but to support this theory a larger patient group must be studied.

MeSH terms

  • Adult
  • Angiotensinogen / genetics*
  • Diabetes Complications / genetics
  • Diabetes Mellitus / genetics*
  • Disease Progression
  • Female
  • Gene Deletion*
  • Genotype
  • Humans
  • Hypertension / genetics
  • Immunosuppressive Agents / pharmacology
  • Kidney Failure, Chronic / complications*
  • Kidney Failure, Chronic / genetics*
  • Kidney Transplantation / adverse effects
  • Kidney Transplantation / methods*
  • Male
  • Middle Aged
  • Peptidyl-Dipeptidase A / genetics*
  • Polymorphism, Genetic*
  • Transplantation, Homologous

Substances

  • Immunosuppressive Agents
  • Angiotensinogen
  • Peptidyl-Dipeptidase A