J Viral Hepat. 2019 Apr 10. doi: 10.1111/jvh.13107. [Epub ahead of print]
Genetic variation in FCER1A predicts peginterferon alfa-2a-induced hepatitis B surface antigen clearance in East Asian patients with chronic hepatitis B.
Wei L1,2, Pavlovic V3, Bansal AT4, Chen X5, Foster GR6, He H3, Kao JH7, Lampertico P8, Liaw YF9, Motoc A10, Papatheodoridis GV11, Piratvisuth T12, Plesniak R13, Wat C3.
Author information
1
Peking University People's Hospital, Beijing, China.
2
Peking University Hepatology Institute, Beijing, China.
3
Roche Products Ltd, Welwyn Garden City, UK.
4
Acclarogen Ltd, Cambridge, UK.
5
Guangdong General Hospital, Guangzhou, China.
6
Queen Mary's University of London, Bart's and The London School of Medicine, London, UK.
7
Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.
8
AM& A Migliavacca Center for Liver Disease, Gastroenterology and Hepatology Unit, , Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Università degli Studi di Milano, Milan, Italy.
9
Liver Research Unit, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taipei, Taiwan.
10
Infectious and Tropical Diseases Hospital "Dr. Victor Babes", Bucharest, Romania.
11
Department of Gastroenterology, Medical School of National & Kapodistrian University of Athens, Laiko General Hospital, Athens, Greece.
12
NKC Institute of Gastroenterology and Hepatology, Prince of Songkla University, Hat-Yai, Thailand.
13
University of Rzeszów, Faculty of Medicine, Clinical Department Of Infectious Diseases, Łańcut, Poland.
Abstract
In a multicenter, genome-wide association study to identify host genetic factors associated with treatment response in adult chronic hepatitis B patients, genotype data were obtained by microarray analysis from 1669 patients who received peginterferon alfa-2a for ≥24 weeks with/without a nucleos(t)ide analog. Treatment response was assessed at least 24 weeks post-treatment, using serological and/or virological endpoints. Thirty-six single-marker analyses and a gene-by-gene analysis were conducted. No single nucleotide polymorphisms (SNPs) achieved genome-wide significance (P<5 × 10-8 ) in single-marker analyses, but suggestive associations (P<1 × 10-5 ) were identified for 116 SNPs. In gene-by-gene analyses, one gene, FCER1A (rs7549785), reached genome-wide significance (P=2.65 × 10-8 ) in East Asian patients for hepatitis B surface antigen (HBsAg) clearance, with a moderate effect size (odds ratio = 4.74). Eleven of 44 carriers (25%) of the A allele at rs7549785 achieved HBsAg clearance compared with 69/1051 (7%) noncarriers. FCER1A encodes the alpha subunit of the immunoglobulin E receptor. In a post hoc analysis of a homogenous patient subset, the strongest intra-genic association was for rs7712322 (POLR3G, P=7.21 × 10-7 ). POLR3G encodes the G subunit of the Polymerase (RNA) III enzyme, involved in sensing and limiting infection by intracellular bacteria and DNA viruses, and as a DNA sensor in innate immune responses. FCER1A (rs7549785), and possibly POLR3G (rs7712322), are shown to be associated with peginterferon alfa-2a response in adult patients with chronic hepatitis B. Independent confirmation of these findings is warranted (clinicaltrials.gov number NCT01855997). This article is protected by copyright. All rights reserved.
This article is protected by copyright. All rights reserved.
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