Association between gene polymorphisms of the components of the renin-angiotensin-aldosteron system, graft function, and the prevalence of hypertension, anemia, and erythrocytosis after kidney transplantation

Transplant Proc. 2011 Oct;43(8):2957-63. doi: 10.1016/j.transproceed.2011.07.016.

Abstract

Introduction: Genetic predisposition, including polymorphisms of the renin-angiotensin system (RAS) genes, are among the potential factors that may affect the occurrence of hypertension, anemia, or erythrocytosis as well as transplanted kidney function. However, the association of the RAS genes polymorphism and the kidney transplant outcomes is controversial. The aim of this study was to analyze the association between polymorphic variants of the angiotensin-converting enzyme (insertion/deletion [I/D]), angiotensinogen (M235T), and angiotensin II receptor type 1 (A1166C) genes, and the early and long-term kidney graft outcomes, as well as the prevalence of hypertension, anemia and erythrocytosis after kidney transplantation.

Patients and methods: We included 331 consecutive kidney transplant patients performed between 1998 and 2003. Of the total, 87.9% of patients completed a 5-year follow-up. Subjects were genotyped for the I/D, M235T, and A1166C polymorphisms.

Results: None of the examined polymorphism affected early or long-term graft function or was associated with hypertension before or after kidney transplantation. There was no significant difference in genotype distribution between patients with and without posttransplant erythrocytosis. However, posttransplant anemia (PTA) seemed to be significantly more common among kidney recipients with TT and MT than MM angiotensinogen genotypes (35.7% vs 20.7%; P=.03). The T allele was associated with the risk of development of PTA (odds ratio, 2.12; 95% confidence interval, 1.12-3.99; P=.02).

Conclusion: Our results do not support the hypothesis that polymorphism of the genes coding RAS components may by an independent risk factor for the development of interstitial fibrosis/tubular atrophy, posttransplant hypertension, or PTE. Further studies are necessary to investigate the association between angiotensinogen M235T genotypes and PTA.

MeSH terms

  • Adult
  • Anemia / etiology*
  • Anemia / genetics
  • Angiotensinogen / genetics
  • Female
  • Follow-Up Studies
  • Genetic Association Studies
  • Graft Survival / genetics
  • Humans
  • Hypertension / etiology*
  • Hypertension / genetics
  • INDEL Mutation
  • Kidney Transplantation / adverse effects*
  • Kidney Transplantation / physiology
  • Male
  • Middle Aged
  • Peptidyl-Dipeptidase A / genetics
  • Polycythemia / etiology*
  • Polycythemia / genetics
  • Polymorphism, Genetic*
  • Polymorphism, Single Nucleotide
  • Receptor, Angiotensin, Type 1 / genetics
  • Renin-Angiotensin System / genetics*
  • Risk Factors

Substances

  • AGTR1 protein, human
  • Receptor, Angiotensin, Type 1
  • Angiotensinogen
  • Peptidyl-Dipeptidase A