Genetic variation in FCER1A predicts peginterferon alfa-2a-induced hepatitis B surface antigen clearance in East Asian patients with chronic hepatitis B

Lai Wei, Vedran Pavlovic, Aruna T. Bansal, Xiaoping Chen, Graham R. Foster, Hua He, Jia Horng Kao, Pietro Lampertico, Yun Fan Liaw, Adriana Motoc, George V. Papatheodoridis, Teerha Piratvisuth, Robert Plesniak, Cynthia Wat

Research output: Contribution to journalArticle

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).

Original languageEnglish
Pages (from-to)1040-1049
JournalJournal of Viral Hepatitis
Volume26
Issue number9
DOIs
Publication statusPublished - Jan 1 2019

Fingerprint

Chronic Hepatitis B
Hepatitis B Surface Antigens
Genes
Single Nucleotide Polymorphism
Genome
RNA Polymerase III
IgE Receptors
DNA Viruses
Genome-Wide Association Study
Microarray Analysis
Innate Immunity
Therapeutics
Alleles
Odds Ratio
Genotype
peginterferon alfa-2a
Bacteria
DNA
Enzymes
Infection

Keywords

  • chronic hepatitis B
  • genetic variation
  • peginterferon alfa-2a
  • response

ASJC Scopus subject areas

  • Hepatology
  • Infectious Diseases
  • Virology

Cite this

Genetic variation in FCER1A predicts peginterferon alfa-2a-induced hepatitis B surface antigen clearance in East Asian patients with chronic hepatitis B. / Wei, Lai; Pavlovic, Vedran; Bansal, Aruna T.; Chen, Xiaoping; Foster, Graham R.; He, Hua; Kao, Jia Horng; Lampertico, Pietro; Liaw, Yun Fan; Motoc, Adriana; Papatheodoridis, George V.; Piratvisuth, Teerha; Plesniak, Robert; Wat, Cynthia.

In: Journal of Viral Hepatitis, Vol. 26, No. 9, 01.01.2019, p. 1040-1049.

Research output: Contribution to journalArticle

Wei, L, Pavlovic, V, Bansal, AT, Chen, X, Foster, GR, He, H, Kao, JH, Lampertico, P, Liaw, YF, Motoc, A, Papatheodoridis, GV, Piratvisuth, T, Plesniak, R & Wat, C 2019, 'Genetic variation in FCER1A predicts peginterferon alfa-2a-induced hepatitis B surface antigen clearance in East Asian patients with chronic hepatitis B', Journal of Viral Hepatitis, vol. 26, no. 9, pp. 1040-1049. https://doi.org/10.1111/jvh.13107
Wei, Lai ; Pavlovic, Vedran ; Bansal, Aruna T. ; Chen, Xiaoping ; Foster, Graham R. ; He, Hua ; Kao, Jia Horng ; Lampertico, Pietro ; Liaw, Yun Fan ; Motoc, Adriana ; Papatheodoridis, George V. ; Piratvisuth, Teerha ; Plesniak, Robert ; Wat, Cynthia. / Genetic variation in FCER1A predicts peginterferon alfa-2a-induced hepatitis B surface antigen clearance in East Asian patients with chronic hepatitis B. In: Journal of Viral Hepatitis. 2019 ; Vol. 26, No. 9. pp. 1040-1049.
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AU - Chen, Xiaoping

AU - Foster, Graham R.

AU - He, Hua

AU - Kao, Jia Horng

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AU - Liaw, Yun Fan

AU - Motoc, Adriana

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