Bogna Ziarkiewicz-Wróblewska1, Emir Sajjad2, Michał Ciszek3, Łukasz Hutnik4, Dominika Łukasik1, Mikołaj Fedorowicz4, Tadeusz Wróblewski5, Waldemar Patkowski5, Leszek Pączek3, Rafał Płoski6, Paweł Włodarski4, Jacek Malejczyk4. 1. Department of Pathology, Center for Biostructure Research, Medical University of Warsaw, Warsaw, Poland. 2. Histology and Embryology, Center for Biostructure Research, Medical University of Warsaw, Warsaw, Poland. 3. Department of Immunology, Transplantology and Internal Medicine, Institute of Transplantology, Medical University of Warsaw, Warsaw, Poland. 4. Department of Histology and Embryology, Center for Biostructure Research, Medical University of Warsaw, Warsaw, Poland. 5. Department of General, Transplant and Liver Surgery, Medical University of Warsaw, Warsaw, Poland. 6. Department of Medical Genetics, Center for Biostructure Research, Medical University of Warsaw, Warsaw, Poland.
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.
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-infectedpatients. 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:Donorrs868 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 donorrs868 SNP located in TGFBR1 3'UTR.
Authors: Emir Ahmed Sajjad; Marek Radkowski; Agnieszka Perkowska-Ptasińska; Marek Pacholczyk; Magdalena Durlik; Mikołaj Fedorowicz; Renata Pietrzak; Bogna Ziarkiewicz-Wróblewska; Paweł Włodarski; Jacek Malejczyk Journal: Ann Transplant Date: 2017-10-24 Impact factor: 1.530