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A pdcd1 role in the genetic predisposition to nafld-hcc?

Lookup NU author(s): Nardeen Eldafashi, Dr Rebecca Darlay, Dr Ruchi Shukla, Misti McCain, Robyn Watson, Dr Yang-Lin Liu, Nikki Mcstraw, Marco Youssef William Zaki, Professor Ann Daly, Joao Mauricio, Professor Alastair Burt, Professor Heather Cordell, Professor Quentin Anstee, Professor Helen Reeves

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This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


Abstract

© 2021 by the authors. Licensee MDPI, Basel, Switzerland.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.


Publication metadata

Author(s): Eldafashi N, Darlay R, Shukla R, McCain MV, Watson R, Liu YL, McStraw N, Fathy M, Fawzy MA, Zaki MYW, Daly AK, Mauricio JP, Burt AD, Haugk B, Cordell HJ, Bianco C, Dufour J-F, Valenti L, Anstee QM, Reeves HL

Publication type: Article

Publication status: Published

Journal: Cancers

Year: 2021

Volume: 13

Issue: 6

Online publication date: 19/03/2021

Acceptance date: 16/03/2021

Date deposited: 29/03/2021

ISSN (electronic): 2072-6694

Publisher: MDPI AG

URL: https://doi.org/10.3390/cancers13061412

DOI: 10.3390/cancers13061412


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