TY - JOUR
TI - Genetic variation in FCER1A predicts peginterferon alfa-2a-induced hepatitis B surface antigen clearance in East Asian patients with chronic hepatitis B
AU - Wei, L.
AU - Pavlovic, V.
AU - Bansal, A.T.
AU - Chen, X.
AU - Foster, G.R.
AU - He, H.
AU - Kao, J.-H.
AU - Lampertico, P.
AU - Liaw, Y.-F.
AU - Motoc, A.
AU - Papatheodoridis, G.V.
AU - Piratvisuth, T.
AU - Plesniak, R.
AU - Wat, C.
JO - Journal of Viral Hepatitis
PY - 2019
VL - 26
TODO - 9
SP - 1040-1049
PB - Wiley-Blackwell Publishing Ltd
SN - 1352-0504, 1365-2893
TODO - 10.1111/jvh.13107
TODO - DNA directed RNA polymerase III;  hepatitis B surface antigen;  immunoglobulin E receptor;  nucleoside analog;  peginterferon alpha2a;  alpha interferon;  antivirus agent;  DNA directed RNA polymerase III;  FCER1A protein, human;  hepatitis B surface antigen;  immunoglobulin E receptor;  macrogol;  peginterferon alpha2a;  POLR3G protein, human;  recombinant protein, adult;  Article;  chronic hepatitis B;  drug efficacy;  East Asian;  FCER1A gene;  female;  gene;  genetic variation;  genome-wide association study;  human;  major clinical study;  male;  microarray analysis;  multicenter study (topic);  pharmacogenetics;  phase 4 clinical trial (topic);  POLR3G gene;  post hoc analysis;  priority journal;  seroconversion;  single nucleotide polymorphism;  treatment response;  allele;  Asian continental ancestry group;  chronic hepatitis B;  clinical trial;  combination drug therapy;  ethnology;  genetics;  immunology;  middle aged;  multicenter study;  phase 4 clinical trial, Adult;  Alleles;  Antiviral Agents;  Asian Continental Ancestry Group;  Drug Therapy, Combination;  Female;  Genetic Variation;  Genome-Wide Association Study;  Hepatitis B Surface Antigens;  Hepatitis B, Chronic;  Humans;  Interferon-alpha;  Male;  Microarray Analysis;  Middle Aged;  Polyethylene Glycols;  Polymorphism, Single Nucleotide;  Receptors, IgE;  Recombinant Proteins;  RNA Polymerase III
TODO - In a multicentre, 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 intragenic 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). © 2019 John Wiley & Sons Ltd
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