Association of 49245A>G (rs868) polymorphism in the 3'UTR of donor TGFBR1 gene with course of hepatitis C following orthotopic liver transplantation

Ann Transplant. 2014 Dec 12:19:643-51. doi: 10.12659/AOT.891119.

Abstract

Background: Terminal hepatitis C is one of the leading indications for orthotopic liver transplantation (OLT). However, hepatitis C virus (HCV) reinfection occurs in almost all recipients and usually leads to progressive fibrosis and graft failure. Transforming growth factor-b (TGF-β) plays a part in transplanted liver cirrhosis, but nothing is known about the possible role of genetic diversity of TGF-β receptor system. Therefore, the aim of our study was to investigate whether genetic variation in 3' untranslated region (3'UTR) of TGF-β receptor type I (TGFBR1) gene is associated with recurrence and severity of hepatitis C and liver fibrosis following OLT in HCV-infected patients.

Material and methods: The study group included 95 chronic hepatitis C patients following OLT. The recipients and donors were genotyped for 49245A>G (rs868) and 51976G>A (rs334349) single nucleotide polymorphisms (SNP).

Results: Donor rs868 AA genotype was strongly associated with worse clinical course of recurrent hepatitis C. The rs868 AA group displayed more severe symptoms of hepatitis C during the follow-up and the fibrosis score in this group was significantly higher 3 years after OLT.

Conclusions: Clinical course of hepatitis C after OLT may depend on donor rs868 SNP located in TGFBR1 3'UTR.

Publication types

  • Evaluation Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3' Untranslated Regions*
  • Adult
  • Aged
  • Female
  • Follow-Up Studies
  • Genetic Markers
  • Genotype
  • Hepatitis C, Chronic / complications
  • Hepatitis C, Chronic / genetics
  • Hepatitis C, Chronic / surgery*
  • Humans
  • Liver Cirrhosis / genetics
  • Liver Cirrhosis / surgery*
  • Liver Cirrhosis / virology
  • Liver Transplantation*
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide*
  • Protein Serine-Threonine Kinases / genetics*
  • Receptor, Transforming Growth Factor-beta Type I
  • Receptors, Transforming Growth Factor beta / genetics*
  • Recurrence
  • Severity of Illness Index
  • Tissue Donors*
  • Transplantation, Homologous
  • Treatment Outcome

Substances

  • 3' Untranslated Regions
  • Genetic Markers
  • Receptors, Transforming Growth Factor beta
  • Protein Serine-Threonine Kinases
  • Receptor, Transforming Growth Factor-beta Type I
  • TGFBR1 protein, human