Investigation of the Association Between the ITPA Gene 94C>A Gene Sequence Variant and Liver Transplant Rejection in Iranian Liver Transplant Recipients

Exp Clin Transplant. 2022 Dec;20(12):1094-1098. doi: 10.6002/ect.2022.0362.

Abstract

Objectives: Inosine triphosphate pyrophosphatase is an enzyme encoded by the ITPA gene and functions to prevent the incorporation of thiopurine nucleotides into DNA and RNA. Thiopurine drug metabolites such as azathioprine and 6-mercaptopurine have been included in the lists of inosine triphosphate pyrophosphatase substrates. Inosine triphosphatase gene alterations are other pharmacogenetic sequence variants possibly involved in thiopurine metabolism. This study aimed to evaluate the possible association between ITPA 94C>A gene sequence variant (C-to-A substitution at nucleotide 94) in liver transplant recipients.

Materials and methods: The genotyping of ITPA 94C>A was evaluated by the polymerase chain reaction- restriction fragment length polymorphism method in 200 liver transplant recipients as well as 100 controls. Data were analyzed with SPSS statistical software.

Results: This study showed statistically significant associations between the CA genotype of the ITPA 94C>A sequence variant and liver transplant in the rejection and nonrejection groups. Moreover, the results reported in this study showed no significant differences between sex, age, and blood group in patients with liver transplant (with or without transplant rejection).

Conclusions: Our results indicated that there were statistically significant associations of the CA genotype of ITPA 94C>A sequence variant with liver transplant in the rejection and nonrejection groups. Further studies are recommended.

MeSH terms

  • Azathioprine
  • Genotype
  • Humans
  • Inosine Triphosphate
  • Iran
  • Liver Transplantation* / adverse effects
  • Pyrophosphatases / genetics
  • Pyrophosphatases / metabolism

Substances

  • Inosine Triphosphate
  • Azathioprine
  • Pyrophosphatases
  • ITPA protein, human