Τίτλος:
Genetic variation in FCER1A predicts peginterferon alfa-2a-induced hepatitis B surface antigen clearance in East Asian patients with chronic hepatitis B
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
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
Συγγραφείς:
Wei, L.
Pavlovic, V.
Bansal, A.T.
Chen, X.
Foster, G.R.
He, H.
Kao, J.-H.
Lampertico, P.
Liaw, Y.-F.
Motoc, A.
Papatheodoridis, G.V.
Piratvisuth, T.
Plesniak, R.
Wat, C.
Περιοδικό:
Journal of Viral Hepatitis
Εκδότης:
Wiley-Blackwell Publishing Ltd
Λέξεις-κλειδιά:
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
