FCER1A的遗传变异预测东亚患有慢性乙型肝炎的聚乙二醇干扰

StephenW

J Viral Hepat. 2019 Apr 10. doi: 10.1111/jvh.13107. [Epub ahead of print]
Genetic variation in FCER1A predicts peginterferon alfa-2a-induced hepatitis B surface antigen clearance in East Asian patients with chronic hepatitis B.
Wei L1,2, Pavlovic V3, Bansal AT4, Chen X5, Foster GR6, He H3, Kao JH7, Lampertico P8, Liaw YF9, Motoc A10, Papatheodoridis GV11, Piratvisuth T12, Plesniak R13, Wat C3.
Author information

1
    Peking University People's Hospital, Beijing, China.
2
    Peking University Hepatology Institute, Beijing, China.
3
    Roche Products Ltd, Welwyn Garden City, UK.
4
    Acclarogen Ltd, Cambridge, UK.
5
    Guangdong General Hospital, Guangzhou, China.
6
    Queen Mary's University of London, Bart's and The London School of Medicine, London, UK.
7
    Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.
8
    AM& A Migliavacca Center for Liver Disease, Gastroenterology and Hepatology Unit, , Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Università degli Studi di Milano, Milan, Italy.
9
    Liver Research Unit, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taipei, Taiwan.
10
    Infectious and Tropical Diseases Hospital "Dr. Victor Babes", Bucharest, Romania.
11
    Department of Gastroenterology, Medical School of National & Kapodistrian University of Athens, Laiko General Hospital, Athens, Greece.
12
    NKC Institute of Gastroenterology and Hepatology, Prince of Songkla University, Hat-Yai, Thailand.
13
    University of Rzeszów, Faculty of Medicine, Clinical Department Of Infectious Diseases, Łańcut, Poland.

Abstract

In a multicenter, 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 intra-genic 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). This article is protected by copyright. All rights reserved.

This article is protected by copyright. All rights reserved.
KEYWORDS:

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

PMID:
    30972912
DOI:
    10.1111/jvh.13107

StephenW

J病毒肝病。 2019年4月10日doi：10.1111 / jvh.13107。 [印刷前的电子版]
FCER1A的遗传变异预测东亚患有慢性乙型肝炎的聚乙二醇干扰素α-2a诱导的乙型肝炎表面抗原清除。
Wei L1,2，Pavlovic V3，Bansal AT4，Chen X5，Foster GR6，He H3，Kao JH7，Lampertico P8，Liaw YF9，Motoc A10，Papatheodoridis GV11，Piratvisuth T12，Plesniak R13，Wat C3。
作者信息

1
    北京大学人民医院，中国北京。
2
    北京大学肝病研究所，中国北京。
3
    罗氏产品有限公司，英国韦林花园城。
4
    Acclarogen Ltd，英国剑桥。
五
    广东省总医院，广州，中国。
6
    玛丽女王大学伦敦大学，巴特大学和伦敦医学院，英国伦敦。
7
    台湾台北大学医院内科
8
    AM＆A Migliavacca肝病，胃肠病学和肝病学中心，Fondazione IRCCS Ca'Granda Ospedale Maggiore Policlinico，意大利米兰米兰大学。
9
    台湾台北长庚大学医学院长庚纪念医院肝脏研究室
10
    传染病和热带病医院“Victor Babes博士”，罗马尼亚布加勒斯特。
11
    雅典国立和卡波迪斯特拉大学医学院消化内科，希腊雅典莱科总医院。
12
    NKC Songkla大学消化内科和肝脏病学研究所，泰国Hat-Yai。
13
    Rzeszów大学，医学院，传染病临床部，波兰Łańcut。

抽象

在一项多中心，全基因组关联研究中，鉴定与成人慢性乙型肝炎患者治疗反应相关的宿主遗传因素，通过微阵列分析获得1669例聚乙二醇干扰素α-2a持续≥24周，有/无核的患者的基因型数据（t）ide模拟。使用血清学和/或病毒学终点，在治疗后至少24周评估治疗反应。进行了36次单标记分析和基因 - 基因分析。在单标记分析中没有单核苷酸多态性（SNP）达到全基因组显着性（P <5×10-8），但鉴定了116个SNP的暗示关联（P <1×10-5）。在逐个基因的分析中，一个基因FCER1A（rs7549785）在东亚患者中获得了乙型肝炎表面抗原（HBsAg）清除的全基因组显着性（P = 2.65×10-8），具有中等效应的大小（优势比= 4.74）。 rs7549785的A等位基因的44个携带者中有11个（25％）实现了HBsAg清除，而非携带者为69/1051（7％）。 FCER1A编码免疫球蛋白E受体的α亚基。在同源患者子集的事后分析中，最强的基因内关联是针对rs7712322（POLR3G，P = 7.21×10-7）。 POLR3G编码聚合酶（RNA）III酶的G亚基，参与感知和限制细胞内细菌和DNA病毒的感染，以及作为先天免疫反应中的DNA传感器。 FCER1A（rs7549785）和可能的POLR3G（rs7712322）显示与成人慢性乙型肝炎患者的聚乙二醇干扰素α-2a反应相关。有必要对这些发现进行独立确认（clinicaltrials.gov编号NCT01855997）。本文受版权保护。版权所有。

本文受版权保护。版权所有。
关键词：

慢性乙型肝炎;遗传变异;聚乙二醇干扰素α-2a;响应

结论：
    30972912
DOI：