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A PDCD1 Role in the Genetic Predisposition to NAFLD-HCC?
Eldafashi, Nardeen; Darlay, Rebecca; Shukla, Ruchi; McCain, Misti Vanette; Watson, Robyn; Liu, Yang Lin; McStraw, Nikki; Fathy, Moustafa; Fawzy, Michael Atef; Zaki, Marco Y W; Daly, Ann K; Maurício, João P; Burt, Alastair D; Haugk, Beate; Cordell, Heather J; Bianco, Cristiana; Dufour, Jean-François; Valenti, Luca; Anstee, Quentin M; Reeves, Helen L.
Affiliation
  • Eldafashi N; Translational and Clinical Research Institute, Faculty of Medical Sciences, The Medical School, Newcastle University, Framlington Place, Newcastle upon Tyne NE2 4HH, UK.
  • Darlay R; Biochemistry Department, Faculty of Pharmacy, Minia University, Minia 61519, Egypt.
  • Shukla R; Population Health Sciences Institute, Faculty of Medical Sciences, Newcastle University, International Centre for Life, Newcastle upon Tyne NE1 3BZ, UK.
  • McCain MV; Biosciences Institute, Faculty of Medical Sciences, The Medical School, Newcastle University, Framlington Place, Newcastle upon Tyne NE2 4HH, UK.
  • Watson R; Translational and Clinical Research Institute, Faculty of Medical Sciences, The Medical School, Newcastle University, Framlington Place, Newcastle upon Tyne NE2 4HH, UK.
  • Liu YL; Translational and Clinical Research Institute, Faculty of Medical Sciences, The Medical School, Newcastle University, Framlington Place, Newcastle upon Tyne NE2 4HH, UK.
  • McStraw N; Translational and Clinical Research Institute, Faculty of Medical Sciences, The Medical School, Newcastle University, Framlington Place, Newcastle upon Tyne NE2 4HH, UK.
  • Fathy M; Biosciences Institute, Faculty of Medical Sciences, The Medical School, Newcastle University, Framlington Place, Newcastle upon Tyne NE2 4HH, UK.
  • Fawzy MA; Biochemistry Department, Faculty of Pharmacy, Minia University, Minia 61519, Egypt.
  • Zaki MYW; Biochemistry Department, Faculty of Pharmacy, Minia University, Minia 61519, Egypt.
  • Daly AK; Translational and Clinical Research Institute, Faculty of Medical Sciences, The Medical School, Newcastle University, Framlington Place, Newcastle upon Tyne NE2 4HH, UK.
  • Maurício JP; Biochemistry Department, Faculty of Pharmacy, Minia University, Minia 61519, Egypt.
  • Burt AD; Translational and Clinical Research Institute, Faculty of Medical Sciences, The Medical School, Newcastle University, Framlington Place, Newcastle upon Tyne NE2 4HH, UK.
  • Haugk B; Translational and Clinical Research Institute, Faculty of Medical Sciences, The Medical School, Newcastle University, Framlington Place, Newcastle upon Tyne NE2 4HH, UK.
  • Cordell HJ; Translational and Clinical Research Institute, Faculty of Medical Sciences, The Medical School, Newcastle University, Framlington Place, Newcastle upon Tyne NE2 4HH, UK.
  • Bianco C; Department of Cellular Pathology, Royal Victoria Infirmary, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle NE1 4LP, UK.
  • Dufour JF; Population Health Sciences Institute, Faculty of Medical Sciences, Newcastle University, International Centre for Life, Newcastle upon Tyne NE1 3BZ, UK.
  • Valenti L; Translational Medicine, Department of Transfusion Medicine and Hematology, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy.
  • Anstee QM; University Clinic for Visceral Surgery and Medicine, University Hospital of Bern, 3010 Bern, Switzerland.
  • Reeves HL; Hepatology, Department of Biomedical Research, University of Bern, 3012 Bern, Switzerland.
Cancers (Basel) ; 13(6)2021 Mar 19.
Article in En | MEDLINE | ID: mdl-33808740
ABSTRACT
Obesity and non-alcoholic fatty liver disease (NAFLD) are contributing to the global rise in deaths from hepatocellular carcinoma (HCC). The pathogenesis of NAFLD-HCC is not well understood. The severity of hepatic steatosis, steatohepatitis and fibrosis are key pathogenic mechanisms, but animal studies suggest altered immune responses are also involved. Genetic studies have so far highlighted a major role of gene variants promoting fat deposition in the liver (PNPLA3 rs738409; TM6SF2 rs58542926). Here, we have considered single-nucleotide polymorphisms (SNPs) in candidate immunoregulatory genes (MICA rs2596542; CD44 rs187115; PDCD1 rs7421861 and rs10204525), in 594 patients with NAFLD and 391 with NAFLD-HCC, from three European centres. Associations between age, body mass index, diabetes, cirrhosis and SNPs with HCC development were explored. PNPLA3 and TM6SF2 SNPs were associated with both progression to cirrhosis and NAFLD-HCC development, while PDCD1 SNPs were specifically associated with NAFLD-HCC risk, regardless of cirrhosis. PDCD1 rs7421861 was independently associated with NAFLD-HCC development, while PDCD1 rs10204525 acquired significance after adjusting for other risks, being most notable in the smaller numbers of women with NAFLD-HCC. The study highlights the potential impact of inter individual variation in immune tolerance induction in patients with NAFLD, both in the presence and absence of cirrhosis.
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Full text: 1 Database: MEDLINE Language: En Year: 2021 Type: Article
Fulltext
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PubMed Links
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Full text: 1 Database: MEDLINE Language: En Year: 2021 Type: Article