PROJECT 3- TOXICOGENOMICS ARISTOLOCHIC ACID NEPHROPATHY

项目 3 - 毒理学马兜铃酸肾病

• 批准号: 8069937
• 负责人: Arthur Patrick Grollman
• 金额: $ 54.94万
• 依托单位: STATE UNIVERSITY NEW YORK STONY BROOK
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-05-05 至 2012-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8069937
• 关键词: Accounting; Acute; Address; Adult; Affect; Archives; Aristolochia; Aristolochic Acids; Balkan Nephropathy; Biological Markers; Blood; Bread; Candidate Disease Gene; Characteristics; Chronic; Chronic Kidney Insufficiency; Collaborations; Control Groups; Controlled Study; Croatia; DNA; DNA Adducts; DNA Repair; Data; Data Set; Databases; Development; Disease; Dose; Enrollment; Epidemiologic Studies; Epidemiology; Exposure to; Fibrosis; Flour; Genes; Genetic; Genetic Polymorphism; Genetic Predisposition to Disease; Genomics; Genotype; Haplotypes; Head; Health Surveys; High Pressure Liquid Chromatography; Inbred Strains Mice; Individual; Ingestion; Inherited; Institutes; Kidney; Kidney Diseases; Leukocytes; Life; Malignant Neoplasms; Maps; Medical; Metabolic Biotransformation; Modeling; Mus; National Institute of Environmental Health Sciences; Nephrology; Nephrotoxic; Nucleotides; Patients; Pattern; Persons; Plants; Poisoning; Predisposition; Public Health; Quantitative Trait Loci; Questionnaires; Recommendation; Relative (related person); Renal function; Research; Research Design; Research Personnel; Resistance; Risk; Rodent; SNP genotyping; Sampling; Serbia; Serum; Specimen; Testing; Tissues; Toxicogenomics; Training; Tumorigenicity; Universities; Urine; Urothelial Cell; Variant; adduct; aristolochic acid I; aristolochic acid II; base; case control; cost; genetic linkage; meetings; mouse model; nephrotoxicity; professor; programs; repaired; tumor

to more than 1,000 adults living in these villages during the spring of 2005. Blood and urine samples were collected from each subject and a detailed questionnaire was administered. These data have now been entered into a database by trained local professionals who have made extensive efforts to check and/or verify information when missing values and suspicious extreme values were observed, returning to the villages to obtain these important data. As a result, missing values have been kept to a minimum and the initial data set, which will be used in the toxicogenomics study, is expected to be ready for formal analysis early in 2007. Serum samples obtained from 1,000 subjects are stored at the Institute of Public Health in Slavonski Brod, Croatia, and the analyses reflecting renal function of these persons are now largely complete. Leukocyte DNAs were extracted by Professor Branko Brdar, a Stony Brook-trained Croatian medical researcher, and his associates. Based on random screens, we have determined that the quality and quantity of DNA extracted from those samples is excellent, permitting us to proceed with the proposed SNP genomic analyses. Our proposal for support to the Center for Inherited Disease Research (CIDR), a centralized facility for SNP genotyping, has been approved by NIEHS. The CIDR expert review panel has reviewed the information contained in Aims 1 & 2 as they relate to genotyping analyses. Their recommendation to assign CIDR staff to participate in this project and to cover most of the costs of genotyping will be considered by the CIDR Board of Governors at their October meeting. Extending our ongoing collaboration with Prof. Xiaomei Li, Head of Nephrology at the University of Beijing, we analyzed 27 samples of exfoliated urothelial cells from patients with documented AAN who are being followed PHS 398/2590 (Rev. 09/04, Reissued 4/2006) Page 155 Continuation Format Page

1,000多名生活在这些村庄的成年人， 2005年的春天。从每个受试者收集血液和尿液样本，并进行详细的问卷调查。 管理。这些数据现已由受过培训的当地专业人员输入数据库， 在缺失值和可疑极端值时，做出了广泛的努力来检查和/或验证信息 他们返回那些村庄，以获得这些重要的数据。因此，缺失值已被 保持在最低限度，预计将用于毒理基因组学研究的初始数据集 2007年初准备进行正式分析。 从1,000名受试者中获得的血清样品储存在Slavonski Brod的公共卫生研究所， 克罗地亚，反映这些人肾功能的分析现已基本完成。白细胞DNA 是由在石溪接受过培训的克罗地亚医学研究员布兰科·布尔达尔教授和他的 合伙人基于随机筛选，我们已经确定提取的DNA的质量和数量 从这些样本中提取的SNP非常好，使我们能够继续进行所提出的SNP基因组分析。我们 支持遗传疾病研究中心（CIDR）的提案，这是一个SNP的集中设施 基因分型，已被NIEHS批准。CIDR专家审查小组审查了信息 包含在目标1和2中，因为它们涉及基因分型分析。他们建议指派CIDR工作人员 参加这个项目，并支付基因分型的大部分费用将由CIDR委员会考虑。 州长们在10月的会议上。 为了扩展我们与北京大学肾脏病学主任李小梅教授的持续合作，我们 分析了27例来自记录的AAN患者的脱落尿路上皮细胞样本， PHS 398/2590（2004年9月修订，2006年4月重新印发）第155页