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dc.contributor.authorSharkawy, REen
dc.contributor.authorBayoumi, Aen
dc.contributor.authorMetwally, Men
dc.contributor.authorMangia, Aen
dc.contributor.authorBerg, Ten
dc.contributor.authorRomero-Gomez, Men
dc.contributor.authorAbate, MLen
dc.contributor.authorIrving, WLen
dc.contributor.authorSheridan, Den
dc.contributor.authorDore, GJen
dc.contributor.authorSpengler, Uen
dc.contributor.authorLampertico, Pen
dc.contributor.authorBugianesi, Een
dc.contributor.authorWeltman, Men
dc.contributor.authorMollison, Len
dc.contributor.authorCheng, Wen
dc.contributor.authorRiordan, Sen
dc.contributor.authorSantoro, Ren
dc.contributor.authorGallego-Durán, Ren
dc.contributor.authorFischer, Jen
dc.contributor.authorNattermann, Jen
dc.contributor.authorD'Ambrosio, Ren
dc.contributor.authorMcLeod, Den
dc.contributor.authorPowell, Een
dc.contributor.authorLatchoumanin, Oen
dc.contributor.authorThabet, Ken
dc.contributor.authorNajim, MAMen
dc.contributor.authorDouglas, MWen
dc.contributor.authorLiddle, Cen
dc.contributor.authorQiao, Len
dc.contributor.authorGeorge, Jen
dc.contributor.authorEslam, Men
dc.contributor.authorInternational Liver Disease Genetics Consortium (ILDGC)en

Hepatocarcinogenesis is tightly linked to liver fibrosis. Recently, two GWAS variants, MICA rs2596542 and DEPDC5 rs1012068 were identified as being associated with the development of HCV-induced hepatocellular carcinoma (HCC) in Japanese patients. The role of these variants on hepatic inflammation and fibrosis that are closely associated with HCC development is not known, nor are the biological mechanisms underlying their impact on the liver. Here, we demonstrate in 1689 patients with chronic hepatitis C (CHC) (1,501 with CHC and 188 with HCV-related HCC), that the MICA (T) allele, despite not being associated with HCC susceptibility, is associated with increased fibrosis stage (OR: 1.47, 95% CI: 1.05-2.06, p = 0.02) and fibrosis progression rate (hazards ratio: 1.41, 95% CI: 1.04-1.90, p = 0.02). The DEPDC5 variant was not associated with any of these phenotypes. MICA expression was down-regulated in advanced fibrosis stages. Further, (T) allele carriage was associated with lower MICA expression in liver and serum. Transforming growth factor-β1 (TGF-β1) expression suppresses MICA expression in hepatic stellate cells. Our findings suggest a novel mechanism linking susceptibility to advanced fibrosis and subsequently indirectly to HCC, to the level of MICA expression through TGF-β1-dependent mechanisms.

dc.format.extent1439 - 1439en
dc.publisherNature Research (part of Springer Nature)en
dc.titleA variant in the MICA gene is associated with liver fibrosis progression in chronic hepatitis C through TGF-β1 dependent mechanisms.en
dc.typeJournal Article
plymouth.journalScientific Reportsen
plymouth.organisational-group/Plymouth/00 Groups by role
plymouth.organisational-group/Plymouth/00 Groups by role/Academics
plymouth.organisational-group/Plymouth/Faculty of Medicine and Dentistry
plymouth.organisational-group/Plymouth/Faculty of Medicine and Dentistry/Biomedical Research Group
plymouth.organisational-group/Plymouth/Faculty of Medicine and Dentistry/Biomedical Research Group/RC Reporting Group BRG
plymouth.organisational-group/Plymouth/Faculty of Medicine and Dentistry/Collaboration for the Advancement of Medical Education Research Assessment
plymouth.organisational-group/Plymouth/REF 2021 Researchers by UoA
plymouth.organisational-group/Plymouth/REF 2021 Researchers by UoA/UoA01 Clinical Medicine
dc.rights.embargoperiodNot knownen
rioxxterms.typeJournal Article/Reviewen

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