Ignite Creation Date:
2024-05-05 @ 4:54 PM
Last Modification Date:
2024-10-26 @ 9:25 AM
Study NCT ID:
NCT00342186
Status:
COMPLETED
Last Update Posted:
2020-06-16
First Post:
2006-06-19
Brief Title:
Genes Involved in Resistance or Susceptibility to Hepatitis B Virus
Sponsor:
National Cancer Institute NCI
Organization:
National Institutes of Health Clinical Center CC
Study Overview
Official Title:
Human Genes Involved in Susceptibility or Resistance to Hepatitis B Virus
Status:
COMPLETED
Status Verified Date:
2020-06
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
This study conducted by the Beijing University First Hospital of China and the National Cancer NCI will try to identify genes associated with either susceptibility or resistance to chronic infection by the hepatitis B virus HBV Some people recover from HBV infection others become chronically infected and may go on to develop severe liver disease such as cirrhosis or liver cancer About 350 million people worldwide have chronic HBV infection Of 120 million infected Chinese 90 percent of children infected at less than 5 years of age and 10 percent of infected adults develop persistent infection
HBV-infected and non-infected healthy persons of Han ethnicity born before 1963 may be eligible for this study Offspring of infected candidates born in any year may also be enrolled Infected adults must have at least one infected parent or sibling Persons who resided in Fusui County of Guangxi Zhuang Autonomous Region or in the Qidong district of Jiangsu Province for at least 6 months before 1986 may not participate
All participants except offspring of the study subjects will fill out a health questionnaire providing information about eating drinking and smoking habits and a personal and family health history and will donate no more than 20 milliliters of blood The blood will be tested for antibodies antigens and other substances that may indicate infection with hepatitis viruses Some of the blood will be sent to the NCI for DNA analysis to identify genetic factors that may influence clearance of the hepatitis virus after infection or progression to liver diseases associated with HBV infection Infected patients who have had a liver biopsy in the past will be asked permission to examine tissue from the biopsy and to review laboratory results of any tests done for diagnostic and treatment purposes
When the study is completed specimens sent to the NCI will have identifiers linking the material to the donor removed The anonymous samples may then be used for other genetic studies Specimens remaining in China will continue to have identifiers linked to them and may be used for future studies designed to identify who is at greatest risk of developing serious liver diseases Participants who do not want their blood used for future studies may request that the samples be destroyed
Because children inherit one-half of their DNA from each parent DNA samples from HBV infected study participants may provide additional information about the parent s DNA structure Offspring who participate in this study will provide a DNA sample The sample is obtained by swishing a mouthwash in the mouth for 30 seconds and then spitting the mouth wash into a cup The DNA is then isolated from the mouth cells
HBV-infected and non-infected healthy persons of Han ethnicity born before 1963 may be eligible for this study Offspring of infected candidates born in any year may also be enrolled Infected adults must have at least one infected parent or sibling Persons who resided in Fusui County of Guangxi Zhuang Autonomous Region or in the Qidong district of Jiangsu Province for at least 6 months before 1986 may not participate
All participants except offspring of the study subjects will fill out a health questionnaire providing information about eating drinking and smoking habits and a personal and family health history and will donate no more than 20 milliliters of blood The blood will be tested for antibodies antigens and other substances that may indicate infection with hepatitis viruses Some of the blood will be sent to the NCI for DNA analysis to identify genetic factors that may influence clearance of the hepatitis virus after infection or progression to liver diseases associated with HBV infection Infected patients who have had a liver biopsy in the past will be asked permission to examine tissue from the biopsy and to review laboratory results of any tests done for diagnostic and treatment purposes
When the study is completed specimens sent to the NCI will have identifiers linking the material to the donor removed The anonymous samples may then be used for other genetic studies Specimens remaining in China will continue to have identifiers linked to them and may be used for future studies designed to identify who is at greatest risk of developing serious liver diseases Participants who do not want their blood used for future studies may request that the samples be destroyed
Because children inherit one-half of their DNA from each parent DNA samples from HBV infected study participants may provide additional information about the parent s DNA structure Offspring who participate in this study will provide a DNA sample The sample is obtained by swishing a mouthwash in the mouth for 30 seconds and then spitting the mouth wash into a cup The DNA is then isolated from the mouth cells
Detailed Description:
Persistent hepatitis B viral HBV infection is a significant public health problem because of the occurence of chronic liver disease cirrhosis and hepatocarcinoma HCC 1-3 Roughly one-third of the world population has been infected with HBV and there are about 350 million 5-6 persistent carriers HBV causes 80 of all liver cancer and is the second most important carcinogen after smoking tobacco There is an approximate 90 risk of becoming a persistent carrier following perinatal infection in infants born to e antigen positive carrier mothers and 30 risk in pre-school children Only 5-10 of adults become persistent carriers following infection Like HIV HBV is transmitted by contaminated blood through transfusion or intravenous drug use and by high-risk sexual behavior
The purpose of this investigation is to study how different outcomes of hepatitis B exposure and infection are affected by host genetic factors in the Chinese population where more than 120 million individuals are infected with HBV Of people persistently infected with HBV 10-30 will develop liver cirrhosis LC and hepatocellular carcinoma HCC These highly variable outcomes in both clearance rates and disease outcomes in persistently infected individuals cannot be fully explained by differences in viral or environmental factors Thus differences in host genetic factors may affect hepatitis B natural history
Blood will be collected from volunteers in China Healthy donors unexposed to HBV or HCV individuals who have cleared HBV and asymptomatic carriers of HBV will be identified by the Peking University hospitals and blood bank HBV infected individuals with chronic hepatitis cirrhosis or HCC will be identified by the Peking University hospital hepatitis clinics Targeted individuals will be asked to participate by letter or a telephone interview by trained hospital staff A database of clinical and family information will be created from a questionnaire completed by hospital staff A database of clinical and family information will be created from a questionnaire completed by hospital staff interviewers Blood will be separated into plasma and peripheral blood mononuclear cells PBMCs and cryopreserved in China Serum will be tested in China for hepatitis viral markers HBV genotypes and HBV viral load Two vials of PBMC will be transferred to the LGD NCI-USA for mRNA expression assays and host genetic analysis Lymphoblastoid cell lines will be established by the LGD-NCI as a source of renewable DNA RNA will be extracted from PBMCs for determination of mRNA expression by the microarray method Results of mRNA expression assays and literature searches will be used to identify candidate genes DNA extracted from cell lines will be genotyped for single nucleotide polymorphisms SNPs in candidate genes and DNA markers including HLA cytokines chomokines and their receptors and putative HBV cell entry targets by DNA genotyping methods SNPs in candidate genes will be identified using public and private SNP databases and SNP discovery methods SNPs will be genotyped study participants and analyzed to detect associations between polymorphisms and phenotypes obtained from clinical and laboratory testing If a genetic marker associated with the development of a disease phenotype is found there are potential applications in diagnostics and therapy The identification of allelic polymorphisms in genes involved in the pathway from chronic viral infection to LC and ultimately HCC would provide insight into the carcinogenic process
The purpose of this investigation is to study how different outcomes of hepatitis B exposure and infection are affected by host genetic factors in the Chinese population where more than 120 million individuals are infected with HBV Of people persistently infected with HBV 10-30 will develop liver cirrhosis LC and hepatocellular carcinoma HCC These highly variable outcomes in both clearance rates and disease outcomes in persistently infected individuals cannot be fully explained by differences in viral or environmental factors Thus differences in host genetic factors may affect hepatitis B natural history
Blood will be collected from volunteers in China Healthy donors unexposed to HBV or HCV individuals who have cleared HBV and asymptomatic carriers of HBV will be identified by the Peking University hospitals and blood bank HBV infected individuals with chronic hepatitis cirrhosis or HCC will be identified by the Peking University hospital hepatitis clinics Targeted individuals will be asked to participate by letter or a telephone interview by trained hospital staff A database of clinical and family information will be created from a questionnaire completed by hospital staff A database of clinical and family information will be created from a questionnaire completed by hospital staff interviewers Blood will be separated into plasma and peripheral blood mononuclear cells PBMCs and cryopreserved in China Serum will be tested in China for hepatitis viral markers HBV genotypes and HBV viral load Two vials of PBMC will be transferred to the LGD NCI-USA for mRNA expression assays and host genetic analysis Lymphoblastoid cell lines will be established by the LGD-NCI as a source of renewable DNA RNA will be extracted from PBMCs for determination of mRNA expression by the microarray method Results of mRNA expression assays and literature searches will be used to identify candidate genes DNA extracted from cell lines will be genotyped for single nucleotide polymorphisms SNPs in candidate genes and DNA markers including HLA cytokines chomokines and their receptors and putative HBV cell entry targets by DNA genotyping methods SNPs in candidate genes will be identified using public and private SNP databases and SNP discovery methods SNPs will be genotyped study participants and analyzed to detect associations between polymorphisms and phenotypes obtained from clinical and laboratory testing If a genetic marker associated with the development of a disease phenotype is found there are potential applications in diagnostics and therapy The identification of allelic polymorphisms in genes involved in the pathway from chronic viral infection to LC and ultimately HCC would provide insight into the carcinogenic process
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 02-C-N323 | None | None | None |