A population-based study to investigate host genetic factors associated with hepatitis B infection and pathogenesis in the Chinese population.
BACKGROUND
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
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.


CONCLUSIONS
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.
Zeng
Zheng
Z
SAIC/Laboratory of Genomic Diversity, National Cancer Institute-Frederick, National Institutes of Health, Frederick, USA. zeng@bjmu.edu.cn
Guan
Li
L
An
Ping
P
Sun
Shan
S
O'Brien
Stephen J
SJ
Winkler
Cheryl A
CA
D044466:Asian People / Q000235:genetics*; D006528:Carcinoma, Hepatocellular / Q000235:genetics; D002353:Carrier State / Q000821:virology; D016022:Case-Control Studies; D006508:Hepatitis Antibodies / Q000097:blood; D006509:Hepatitis B / Q000453:epidemiology*; D006511:Hepatitis B Antigens / Q000097:blood; D019694:Hepatitis B, Chronic / Q000235:genetics; D054884:Host-Pathogen Interactions; D006801:Humans; D008103:Liver Cirrhosis / Q000235:genetics; D008111:Liver Function Tests; D011110:Polymorphism, Genetic; D012107:Research Design; D012307:Risk Factors; D011795:Surveys and Questionnaires
D006508:Hepatitis Antibodies; D006511:Hepatitis B Antigens