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Nat Commun. 2015 Mar 5;6:6422. doi: 10.1038/ncomms7422.

Interferon-λ rs12979860 genotype and liver fibrosis in viral and non-viral chronic liver disease.

Author information

1
Storr Liver Unit, Westmead Millennium Institute and Westmead Hospital, University of Sydney, Sydney, New South Wales 2145, Australia.
2
Faculty of Engineering, Department of Systems and Biomedical Engineering, Minia University, Minia 6111, Egypt.
3
1] Storr Liver Unit, Westmead Millennium Institute and Westmead Hospital, University of Sydney, Sydney, New South Wales 2145, Australia [2] Institute of Immunology and Allergy Research, Westmead Hospital and Westmead Millennium Institute, University of Sydney, Sydney, New South Wales 2145, Australia.
4
Unit for The Clinical Management of Digestive Diseases and CIBERehd, Hospital Universitario de Valme, Sevilla 41014, Spain.
5
1] Medizinische Klinik m.S. Hepatologie und Gastroenterologie, Charite, Campus Virchow-Klinikum, Universitätsmedizin Berlin, Berlin 04103, Germany [2] Department of Hepatology, Clinic for Gastroenterology and Rheumatology, University Clinic Leipzig, Leipzig 04103, Germany.
6
1] Kirby Institute, The University of New South Wales, Sydney, New South Wales 2052, Australia [2] St Vincent's Hospital, Sydney, New South Wales 2052, Australia.
7
Department of Medicine and Therapeutics, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, China.
8
NIHR Biomedical Research Unit in Gastroenterology and the Liver, University of Nottingham, Nottingham NG7 2UH, UK.
9
1] Liver Research Group, Institute of Cellular Medicine, Medical School, Newcastle University, Newcastle upon Tyne NE2 4HH, UK [2] Institute of Translational and Stratified Medicine, Plymouth University, Plymouth PL4 8AA, UK.
10
Division of Gastroenterology and Hepatology, Department of Medical Science, University of Turin, Turin 10126, Italy.
11
School of Medicine and Pharmacology, Sir Charles Gairdner Hospital Unit, University of Western Australia, Nedlands, Western Australia 6009, Australia.
12
Division of Hepatology, Ospedale Casa Sollievo della Sofferenza, IRCCS, San Giovanni Rotondo 71013, Italy.
13
Department of Gastroenterology and Hepatology, Nepean Hospital, Sydney, New South Wales 2747, Australia.
14
Department of Internal Medicine I, University of Bonn, Bonn 53105, Germany.
15
Faculty of Medicine, Medical Biochemistry and Molecular Biology Department, Cairo University, Cairo 11562, Egypt.
16
Medizinische Klinik m.S. Hepatologie und Gastroenterologie, Charite, Campus Virchow-Klinikum, Universitätsmedizin Berlin, Berlin 04103, Germany.
17
Department of Gastroenterology and Hepatology, Fremantle Hospital, Fremantle, Western Australia 6160, Australia.
18
Department of Gastroenterology and Hepatology, Royal Perth Hospital, Perth, Western Australia 6000, Australia.
19
1] Department of Gastroenterology and Hepatology, Princess Alexandra Hospital, Woolloongabba, Queensland 4102, Australia [2] The University of Queensland, School of Medicine, Princess Alexandra Hospital, Woolloongabba, Queensland 4072, Australia.
20
Gastrointestinal and Liver Unit, Prince of Wales Hospital and University of New South Wales, Sydney, New South Wales 2031, Australia.
21
Department of Anatomical Pathology, Institute of Clinical Pathology and Medical Research (ICPMR), Westmead Hospital, Sydney, New South Wales 2145, Australia.
22
School of Mathematics and Statistics, University of Sydney, Sydney, New South Wales 2006, Australia.
23
Institute of Immunology and Allergy Research, Westmead Hospital and Westmead Millennium Institute, University of Sydney, Sydney, New South Wales 2145, Australia.
24
Liver Research Group, Institute of Cellular Medicine, Medical School, Newcastle University, Newcastle upon Tyne NE2 4HH, UK.
25
Kirby Institute, The University of New South Wales, Sydney, New South Wales 2052, Australia.
26
The Kirby Institute, University of New South Wales, Sydney, New South Wales 2033, Australia.
27
Department of Gastroenterology and Hepatology, Princess Alexandra Hospital, Woolloongabba, Queensland 4102, Australia.

Abstract

Tissue fibrosis is a core pathologic process that contributes to mortality in ~45% of the population and is likely to be influenced by the host genetic architecture. Here we demonstrate, using liver disease as a model, that a single-nucleotide polymorphism (rs12979860) in the intronic region of interferon-λ4 (IFNL4) is a strong predictor of fibrosis in an aetiology-independent manner. In a cohort of 4,172 patients, including 3,129 with chronic hepatitis C (CHC), 555 with chronic hepatitis B (CHB) and 488 with non-alcoholic fatty liver disease (NAFLD), those with rs12979860CC have greater hepatic inflammation and fibrosis. In CHC, those with rs12979860CC also have greater stage-constant and stage-specific fibrosis progression rates (P<0.0001 for all). The impact of rs12979860 genotypes on fibrosis is maximal in young females, especially those with HCV genotype 3. These findings establish rs12979860 genotype as a strong aetiology-independent predictor of tissue inflammation and fibrosis.

PMID:
25740255
PMCID:
PMC4366528
DOI:
10.1038/ncomms7422
[Indexed for MEDLINE]
Free PMC Article

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