Complete sequencing in drug-induced liver injury

药物性肝损伤的完整测序

基本信息

批准号：
8092671
负责人：
Thomas Jacob Urban
金额：
$ 23.31万
依托单位：
DUKE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-07-01 至 2012-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8092671
关键词：
Adverse reactions Alleles Amoxicillin Amoxicillin-Potassium Clavulanate Combination Antibiotics Bioinformatics Biological Child Clavulanate Clinic Clinical Combined Antibiotics DNA Resequencing Databases Detection Development Drug toxicity Drug usage Enrollment Evaluation Event Floxacillin Frequencies Future Genetic Genetic Markers Genetic Predisposition to Disease Genetic Variation Genome Genotype HLA-B Antigens HLA-DRB1 Haplotypes Health Health Care Costs Hepatotoxicity Human Genome Incidence Individual Injury Institutes Laboratories Liver MHC Class II Genes Other Genetics Pathway interactions Patients Penetrance Pharmaceutical Preparations Phenotype Reaction Reporting Risk Safety Sample Size Science Policy Serious Adverse Event Societies Testing Therapeutic Toxic effect Variant Withdrawal acute drug induced liver toxicity case control cohort cost drug development drug market experience genetic risk factor genetic variant genome sequencing genome wide association study health care delivery improved novel public health relevance

项目摘要

DESCRIPTION (provided by applicant): Many generally safe drugs result in severe acute liver injury (drug-induced liver injury, or DILI) in a small percentage of patients. This study seeks to increase our understanding of the genetic risk factors for these events by whole-genome sequencing of 30 individuals experiencing DILI due to the antibiotic combination amoxicillin/clavulanate, discovering novel rare genetic variants, and testing these for association with injury status in a large cohort of DILI cases and controls. This has the potential to identify predictive genetic markers for identification of patients at risk for DILI and, thus, greatly improve the safety of the associated drugs and inform future drug development. PUBLIC HEALTH RELEVANCE: The proposed project seeks to improve our understanding of the genetic factors that contribute to drug-induced liver injury, so as to avoid this severe adverse reaction in patients at risk, and to inform future drug development

描述（由申请人提供）：许多通常安全的药物会导致一小部分患者的严重急性肝损伤（药物诱导的肝损伤或DILI）。这项研究旨在通过全基因组测序对这些事件的遗传危险因素的理解来通过全基因组测序的30个人的全基因组测序，这是由于抗生素组合抗生素组合而经历了DILI，发现了新的稀有遗传变异，并测试了这些新颖的稀有遗传变异大量的DILI病例和对照组。这有可能识别预测性遗传标记，以鉴定有DILI风险的患者，从而大大提高了相关药物的安全性并为未来的药物开发提供了信息。公共卫生相关性：拟议的项目旨在提高我们对导致药物引起的肝损伤的遗传因素的理解