Angiotensinogen polymorphisms and post-transplantation diabetes mellitus in Korean renal transplant subjects

Kidney Blood Press Res. 2013;37(2-3):95-102. doi: 10.1159/000343404. Epub 2013 Mar 31.

Abstract

Background: Post-transplant diabetes mellitus (PTDM) is a common and serious metabolic complication. Genetic polymorphisms of angiotensin-converting enzyme (ACE) and angiotensinogen (AGT) genes have been reported to be related to diabetes mellitus and insulin sensitivity; however, the role of these genes in the development of PTDM is not known. For this purpose, we investigated the association of ACE and AGT genetic polymorphisms with PTDM.

Methods: A total of 302 subjects without previously diagnosed diabetes who had received kidney transplants were included. One ACE single nucleotide polymorphism (SNP) (rs4291) and two AGT SNPs (rs 699 and rs 4762) were genotyped from genomic DNA with direct sequencing.

Results: PTDM developed in 49 (16.2%) of 302 subjects. Subjects in the PTDM were older than those in the non-PTDM. There was a significant difference between the two groups in tacrolimus use (p=0.03). Of the three SNPs, the rs4762 of the AGT gene was significantly associated with the development of PTDM in the dominant models (p = 0.03) after adjusting for age and tacrolimus usage.

Conclusions: AGT gene rs4762 polymorphisms may serve as genetic markers for the development of PTDM. The exact molecular mechanisms still need to be clarified.

MeSH terms

  • Aged
  • Angiotensinogen / genetics*
  • Asian People
  • DNA Primers
  • Diabetes Mellitus / epidemiology
  • Diabetes Mellitus / genetics*
  • Female
  • Gene Frequency
  • Genotype
  • Haplotypes
  • Humans
  • Immunosuppressive Agents / adverse effects
  • Immunosuppressive Agents / therapeutic use
  • Kidney Transplantation / statistics & numerical data*
  • Male
  • Middle Aged
  • Peptidyl-Dipeptidase A / genetics
  • Polymerase Chain Reaction
  • Polymorphism, Genetic / genetics*
  • Polymorphism, Single Nucleotide / genetics
  • Postoperative Complications / epidemiology
  • Postoperative Complications / genetics
  • Republic of Korea / epidemiology
  • Tacrolimus / adverse effects
  • Tacrolimus / therapeutic use

Substances

  • DNA Primers
  • Immunosuppressive Agents
  • Angiotensinogen
  • Peptidyl-Dipeptidase A
  • Tacrolimus