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）：在感染了2 - 3年后，估计有400万美国人患有丙型肝炎感染（HCV）的美国人中有20-30％被预计将发展晚期纤维化和肝硬化。促进纤维化风险因素（如酗酒）的暴露差异可能解释了纤维化风险的某些差异。但是，当前的研究表明，遗传因素也可能影响HCV患者晚期纤维化的风险。研究反复证明与晚期肝病发展有关的两个因素是男性性别和腹部肥胖。但是，包括与男性性激素受体或雄激素受体（AR）有关的特定作用遗传因素以及与腹部肥胖相关的胰岛素抵抗（IR）的特定作用可能尚不清楚。拟议的研究的目的是确定AR和IR基因在增加晚期纤维化风险中的变化的作用。相关的特定目的是：1）识别和收集有关HCV感染的大型男性退伍军人队列的数据； 2）检验以下假设：“高风险”与IR单独或与腹部肥胖相关的基因的变异变异增加了纤维化的风险； 3）检验以下假说，即与AR相关的基因的“高风险”变异也会增加纤维化的风险。AIM 1将与COREDECHERID and CORDECHESS一起识别，并将其用于迈克尔的目标。通过一项病例对照研究，将具有晚期纤维化（病例）的队列成员与有轻度纤维化的组件进行比较（对照）。疾病。