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Genetic Epidemiology of HCV-related Liver Disease

HCV 相关肝病的遗传流行病学

基本信息

批准号：
7514173
负责人：
Donna Lorraine White
金额：
$ 15.79万
依托单位：
BAYLOR COLLEGE OF MEDICINE
依托单位国家：
美国
项目类别：
财政年份：
2008
资助国家：
美国
起止时间：
2008-09-15 至 2013-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7514173
关键词：
Address Advanced Development Alcohol abuse Alcohol consumption American Androgen Receptor Androgens Award Binding Proteins Biological Biopsy Specimen Blood CAG repeat Case-Control Studies Central obesity Chronic Cirrhosis Collection DNA Data Deposition Development Diabetes Mellitus Digestive System Disorders Elevation Enrollment Environment Environmental Exposure Environmental Risk Factor Epidemic Epidemiologic Methods Evaluation Exposure to Fatty Liver Fatty acid glycerol esters Fibrosis Foundations Future Gastroenterology Gender Gene Expression Genes Genetic Genetic Polymorphism Genetic Variation Genotype Goals Gonadal Steroid Hormones Health Hepatitis B Hepatitis C Hepatitis C virus Hormone Receptor Hydroxysteroid Dehydrogenases Individual Infection Inflammation Injury Insulin Resistance Insulin Resistance Pathway Joints Leptin Leukocytes Link Liver Liver Fibrosis Liver diseases Measures Mediating Medical center Mentors Messenger RNA Metabolic Pathway Methods Molecular Epidemiology Molecular Genetics Necrosis Newly Diagnosed Numbers Obesity Outcome Pathogenesis Pathologist Pathway interactions Patients Peripheral Peroxisome Proliferator-Activated Receptors Play Polycystic Ovary Syndrome Predisposition Primary Health Care Primary carcinoma of the liver cells Principal Investigator RNA Receptor Gene Regulatory Element Relative Risks Research Research Personnel Risk Risk Factors Role Sampling Score Serological Severities Specimen Standards of Weights and Measures Steatohepatitis Sterols Susceptibility Gene Testing Testosterone Texas Training Variant Veterans Woman Work abdominal fat adiponectin base cohort endophenotype gene environment interaction gene interaction genetic association genetic epidemiology liver biopsy male member men microsomal triglyceride transfer protein novel oncology peripheral blood programs prospective receptor response skills

项目摘要

DESCRIPTION (provided by applicant): An estimated 20-30% of the four million Americans with hepatitis C infection (HCV) are projected to develop advanced fibrosis and cirrhosis after 2-3 decades of infection. Differences in exposure to fibrosis-promoting risk factors like alcohol abuse likely explain some of this difference in fibrosis risk. However, current research suggests that genetic factors may also influence the risk of advanced fibrosis in HCV patients. Two factors that research has repeatedly shown to be associated with development of advanced liver disease are male gender and abdominal obesity. However, the specific role genetic factors, including those related to male sex hormone receptor or androgen receptors (AR) and to insulin resistance (IR) associated with abdominal obesity, may play in fibrosis risk remains unclear. The goal of the proposed study is to ascertain the role that changes in AR and IR genes play in increasing risk of advanced fibrosis. The associated specific aims are: 1) to identify and collect data on a large and representative cohort of male veterans with HCV infection; 2) to test the hypothesis that 'high risk" variants of genes related to IR either alone or in conjunction with abdominal obesity increase fibrosis risk; and 3) to test the hypothesis that 'high risk' variants of genes related to AR also increase fibrosis risk. Aim 1 will be accomplished with standard epidemiology methods for cohort identification and will be performed at the Michael E. DeBakey VA. Aims 2 and 3 will be addressed through a case-control study in which cohort members with advanced fibrosis (cases) are compared to those with mild fibrosis (controls). The research plan, didactic training and outstanding mentoring environment will work together to allow the principal investigator to acquire new skills as well as refine existing skills in the development and execution of novel genetic epidemiology studies, allowing her to develop into an independent investigator in genetic epidemiology of chronic liver and digestive disorders.

描述（由申请人提供）：