@article{3000522,
    title = "Genetic variation in FCER1A predicts peginterferon alfa-2a-induced hepatitis B surface antigen clearance in East Asian patients with chronic hepatitis B",
    author = "Wei, L. and Pavlovic, V. and Bansal, A.T. and Chen, X. and Foster, G.R. and He, H. and Kao, J.-H. and Lampertico, P. and Liaw, Y.-F. and Motoc, A. and Papatheodoridis, G.V. and Piratvisuth, T. and Plesniak, R. and Wat, C.",
    journal = "Journal of Viral Hepatitis",
    year = "2019",
    volume = "26",
    number = "9",
    pages = "1040-1049",
    publisher = "Wiley-Blackwell Publishing Ltd",
    issn = "1352-0504, 1365-2893",
    doi = "10.1111/jvh.13107",
    keywords = "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",
    abstract = "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"
}