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Please use this identifier to cite or link to this item: http://repository.li.mahidol.ac.th/dspace/handle/123456789/51310
Title: Genome-wide Association Study Identifies Genetic Variants Associated with Early and Sustained Response to (Pegylated) Interferon in Chronic Hepatitis B Patients: The GIANT-B Study
Authors: Willem P. Brouwer
Henry L.Y. Chan
Pietro Lampertico
Jinlin Hou
Pisit Tangkijvanich
Hendrik W. Reesink
Wenhong Zhang
Alessandra Mangia
Tawesak Tanwandee
Giuseppe Montalto
Kris Simon
Necati Ormeci
Liang Chen
Fehmi Tabak
Fulya Gunsar
Robert Flisiak
Peter Ferenci
Meral Akdogan
Filiz Akyuz
Nattiya Hirankarn
Louis Jansen
Vincent Wai Sun Wong
Roberta Soffredini
Xieer Liang
Shalom Chen
Zwier M.A. Groothuismink
Rosanna Santoro
Jerzy Jaroszewicz
Resat Ozaras
Karin Kozbial
Mayur Brahmania
Qing Xie
Watcharasak Chotiyaputta
Qi Xun
Monika Pazgan-Simon
Erkin Oztas
Elke Verhey
Noé R. Montanari
Jian Sun
Bettina E. Hansen
Andre Boonstra
Harry L.A. Janssen
Bettina Hansen
Harry Janssen
Heng Chi
Milan Sonneveld
Rob De Knegt
Henry Chan
Vincent Wong
Grace Wong
Pietro Lampertico
Marta Borghi
Alessandro Loglio
Jinlin Hou
Jian Sun
Xieer Liang
Pisit Tangkijvanich
Nattiya Hirankarn
Pimpayao Sodsai
Natthaya Chuaypen
Henk Reesink
Wenhong Zhang
Shalom Chen
Alessandra Mangia
Rosanna Santoro
Guiseppe Montalto
Kris Simon
Liang Chen
Xi Qun
Robert Flisiak
Jerzy Jaroszewicz
Peter Ferenci
Erkin Oztas
Filiz Akyuz
Jordan Feld
Seham Noureldin
Simin Guo
Qing Xie
Shanghai Jiao Tong University School of Medicine
IRCCS Casa Sollievo della Sofferenza
Erasmus MC
Università degli Studi di Milano
Chulalongkorn University
Slaski Uniwersytet Medyczny w Katowicach
Uniwersytet Medyczny w Bialymstoku
Toronto General Hospital
Università degli Studi di Palermo
Ankara Üniversitesi
Istanbul Üniversitesi Tıp Fakültesi
Medizinische Universitat Wien
Faculty of Medicine, Siriraj Hospital, Mahidol University
Fudan University
Ege University Medical School
Wroclaw Medical University
Chinese University of Hong Kong
Amsterdam UMC - University of Amsterdam
Yuksek Ihsitas Hospital
Cerrahpasa Medical Faculty
Southern Medical University
Keywords: Medicine
Issue Date: 13-Nov-2019
Citation: Clinical Infectious Diseases. Vol.69, No.11 (2019), 1969-1979
Abstract: © 2019 The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America. Background: (Pegylated) Interferon ([Peg]IFN) therapy leads to response in a minority of chronic hepatitis B (CHB) patients. Host genetic determinants of response are therefore in demand. Methods: In this genome-wide association study (GWAS), CHB patients, treated with (Peg)IFN for at least 12 weeks ± nucleos(t)ide analogues within randomized trials or as standard of care, were recruited at 21 centers from Europe, Asia, and North America. Response at 24 weeks after (Peg)IFN treatment was defined as combined hepatitis B e antigen (HBeAg) loss with hepatitis B virus (HBV) DNA <2000 IU/mL, or an HBV DNA <2000 IU/mL for HBeAg-negative patients. Results: Of 1144 patients, 1058 (92%) patients were included in the GWAS analysis. In total, 282 (31%) patients achieved the response and 4% hepatitis B surface antigen (HBsAg) loss. GWAS analysis stratified by HBeAg status, adjusted for age, sex, and the 4 ancestry components identified PRELID2 rs371991 (B= -0.74, standard error [SE] = 0.16, P = 3.44 ×10-6) for HBeAg-positive patients. Importantly, PRELID2 was cross-validated for long-term response in HBeAg-negative patients. G3BP2 rs3821977 (B = 1.13, SE = 0.24, P = 2.46 × 10-6) was associated with response in HBeAg-negative patients. G3BP2 has a role in the interferon pathway and was further examined in peripheral blood mononuclear cells of healthy controls stimulated with IFNα and TLR8. After stimulation, less production of IP-10 and interleukin (IL)-10 proteins and more production of IL-8 were observed with the G3BP2 G-allele. Conclusions: Although no genome-wide significant hits were found, the current GWAS identified genetic variants associated with (Peg)IFN response in CHB. The current findings could pave the way for gene polymorphism-guided clinical counseling, both in the setting of (Peg)IFN and the natural history, and possibly for new immune-modulating therapies. Clinical Trials Registation: NCT01401400.
URI: http://repository.li.mahidol.ac.th/dspace/handle/123456789/51310
metadata.dc.identifier.url: https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85070654880&origin=inward
ISSN: 15376591
10584838
Appears in Collections:Scopus 2019

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