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

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).

• Authors: 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
• Journal: Journal of viral hepatitis (J Viral Hepat) Vol. 26 Issue 9 Pg. 1040-1049 (09 2019) ISSN: 1365-2893 [Electronic] England
• PMID: 30972912 (Publication Type: Clinical Trial, Phase IV, Journal Article, Multicenter Study, Observational Study, Research Support, Non-U.S. Gov't)
• Copyright: © 2019 John Wiley & Sons Ltd.

Chemical References

• Antiviral Agents
• FCER1A protein, human
• Hepatitis B Surface Antigens
• Interferon-alpha
• Receptors, IgE
• Recombinant Proteins
• Polyethylene Glycols
• POLR3G protein, human
• RNA Polymerase III
• peginterferon alfa-2a

Topics

• Adult
• Alleles
• Antiviral Agents (therapeutic use)
• Asian People
• Drug Therapy, Combination
• Female
• Genetic Variation
• Genome-Wide Association Study
• Hepatitis B Surface Antigens (immunology)
• Hepatitis B, Chronic (drug therapy, ethnology, genetics)
• Humans
• Interferon-alpha (therapeutic use)
• Male
• Microarray Analysis
• Middle Aged
• Polyethylene Glycols (therapeutic use)
• Polymorphism, Single Nucleotide
• RNA Polymerase III (genetics)
• Receptors, IgE (genetics, immunology)
• Recombinant Proteins (therapeutic use)