Zeng Zheng, Guan Li, An Ping, Sun Shan, O'Brien Stephen J, Winkler Cheryl A
SAIC/Laboratory of Genomic Diversity, National Cancer Institute-Frederick, National Institutes of Health, Frederick, USA.
BMC Infect Dis. 2008 Jan 2;8:1. doi: 10.1186/1471-2334-8-1.
Hepatitis B virus (HBV) infection is a significant public health problem that may lead to chronic liver disease, cirrhosis, and hepatocellular carcinoma (HCC). Approximately 30% of the world's population has been infected with HBV and approximately 350 million (5-6%) are persistent carriers. More than 120 million Chinese are infected with HBV. The role of host genetic factors and their interactions with environmental factors leading to chronic HBV infection and its complications are not well understood. We believe that a better understanding of these factors and interactions will lead to more effective diagnostic and therapeutic options.
METHODS/DESIGN: This is a population-based, case-control study protocol to enroll 2200 Han Chinese from medical centers in northern and western China. Adult subjects in the following groups are being enrolled: healthy donors (n = 200), HBV infected persons achieving virus clearance (n = 400), asymptomatic HBV persistent carriers (n = 400), chronic hepatitis B cases (n = 400), decompensated liver cirrhosis with HBV infection cases (n = 400), and hepatocellular carcinoma with HBV infection cases (n = 400). In addition, for haplotype inference and quality control of sample handling and genotyping results, children of 1000 cases will be asked to provide a buccal sample for DNA extraction. With the exception of adult patients presenting with liver cirrhosis or HCC, all other cases and controls will be 40 years or older at enrollment. A questionnaire is being administered to capture dietary and environmental risk factors. Both candidate-gene and genome-wide association approaches will be used to assess the role of single genetic factors and higher order interactions with other genetic or environmental factors in HBV diseases.
This study is designed and powered to detect single gene effects as well as gene-gene and environmental-gene interactions. The identification of allelic polymorphisms in genes involved in the pathway leading to chronic viral infection, liver cirrhosis and, ultimately, hepatocellular carcinoma would provide insights to those factors leading to HBV replication, liver inflammation, fibrosis, and the carcinogenic process. An understanding of the contribution of host genetic factors and their interactions may inform public health policy, improve diagnostics and clinical management, and provide targets for drug development.
乙型肝炎病毒（HBV）感染是一个重大的公共卫生问题，可能导致慢性肝病、肝硬化和肝细胞癌（HCC）。世界上约30%的人口曾感染过HBV，约3.5亿人（5%-6%）为持续携带者。超过1.2亿中国人感染了HBV。宿主遗传因素及其与环境因素相互作用在导致慢性HBV感染及其并发症方面所起的作用尚未完全明确。我们认为，更好地了解这些因素及其相互作用将带来更有效的诊断和治疗选择。
方法/设计：这是一项基于人群的病例对照研究方案，将从中国北方和西部的医疗中心招募2200名汉族人。招募以下几组成年受试者：健康供者（n = 200）、实现病毒清除的HBV感染者（n = 400）、无症状HBV持续携带者（n = 400）、慢性乙型肝炎病例（n = 400）、HBV感染所致失代偿期肝硬化病例（n = 400）以及HBV感染所致肝细胞癌病例（n = 400）。此外，为了进行单倍型推断以及样本处理和基因分型结果的质量控制，将要求1000例病例的子女提供口腔拭子样本用于DNA提取。除了患有肝硬化或HCC的成年患者外，所有其他病例和对照在入组时年龄均在40岁及以上。正在进行问卷调查以获取饮食和环境风险因素。将采用候选基因和全基因组关联方法来评估单个遗传因素以及与其他遗传或环境因素的高阶相互作用在HBV疾病中的作用。
本研究的设计和效能旨在检测单基因效应以及基因-基因和环境-基因相互作用。鉴定参与导致慢性病毒感染、肝硬化以及最终肝细胞癌途径的基因中的等位基因多态性，将为那些导致HBV复制、肝脏炎症、纤维化和致癌过程的因素提供见解。了解宿主遗传因素的作用及其相互作用可能为公共卫生政策提供依据，改善诊断和临床管理，并为药物开发提供靶点。
