Genetic variation in T-cell regulatory molecules and JRA

T 细胞调节分子和 JRA 的遗传变异

• 批准号: 7764527
• 负责人: SAMPATH PRAHALAD
• 金额: $ 5.95万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-09-01 至 2010-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7764527
• 关键词: Adolescent; Adult; Affect; Africa South of the Sahara; Arthritis; Asia; Autoimmune Diseases; Autoimmune Process; Award; Biological; Candidate Disease Gene; Child; Childhood; Chronic; Chronic Childhood Arthritis; Chronic Disease; Clinical; Clinical Investigator; Clinical Research; Collection; Complex; Condition; Core Facility; Cystic Fibrosis; Data; Databases; Disease; Environment; Ethnic Origin; Etiology; Europe; Failure; Far East; Funding; Future; Gene Structure; Genes; Genetic; Genetic Models; Genetic Polymorphism; Genetic Variation; Genome; Glass; Goals; Haplotypes; Hemophilia A; Individual; Inherited; Insulin-Dependent Diabetes Mellitus; Investigation; Knowledge; Life; Ligands; Link; Major Histocompatibility Complex Gene; Mentors; Muscular Dystrophies; Numbers; Parents; Pathogenesis; Patients; Pattern; Phenotype; Play; Population Study; Predisposition; Proteins; Registries; Research; Research Design; Research Training; Resources; Rheumatism; Rheumatoid Arthritis; Risk; Role; Scientist; Severity of illness; Sickle Cell Anemia; Single Nucleotide Polymorphism; Structure; T cell regulation; T-Lymphocyte; Test Result; Testing; Time; Training Programs; Translations; Treatment outcome; United States National Institutes of Health; Universities; University Hospitals; Utah; Variant; base; cohort; design; experience; genetic variant; human disease; improved; insight; proband; programs; receptor; response; statistics

DESCRIPTION (provided by applicant): Juvenile rheumatoid arthritis (JRA) is one of the most common chronic conditions of children affecting approximately 50,000 children in the U.S. The etiology and pathogenesis of JRA is complex, though there is clearly a genetic component. Associations between the genes of the major histocompatibility complex and susceptibility to JRA are well established, though identification of causal genetic variants, much less translation to improve clinical practice has not been forthcoming. Over the last decade, direct and indirect evidence has pointed to a role of activated T-cells, particularly of the Th1 phenotype in the pathogenesis of JRA. The goal of this project is to determine whether genetic variation in genes encoding T-cell regulatory molecules contributes to variation in JRA susceptibility, pathogenesis and treatment outcome. This will be accomplished via two specific aims. 1. Analyze genetic diversity in genes encoding ligand-receptor pairs involved in T-cell regulation. 2. Test for association and linkage between the genetic variants identified and susceptibility to JRA and or/variable expressivity of JRA. These studies will be conducted using 3 different cohorts representing the largest collection of JRA patients in the U.S.: (1)140 sibpairs with JRA (2) 500 singletons with JRA and their parents and (3) cases newly ascertained from a registry of more than 650 JRA patients living in the Intermountain West. A five year mentored program is proposed that will incorporate both didactic and research training and will be guided by two established scientists at the University of Utah. Through a NIH funded K30 award, the University of Utah General Clinical Research Center provides a unique didactic program of training in clinical research focused on the inherited basis of human disease. This program incorporates access to resources such as multi-user core facilities, large research centers at the University, and a designated unit in the University Hospital, with specific mentored intensive research experience for maturing clinical investigators. Thus, the University of Utah provides an ideal environment for maximizing the potential of this study and this applicant.

描述(由申请人提供)： 幼年类风湿性关节炎(JRA)是儿童最常见的慢性疾病之一，在美国约有50,000名儿童受到影响。JRA的病因和发病机制很复杂，尽管有明显的遗传成分。主要组织相容性复合体的基因与JRA易感性之间的关系已经得到了很好的证实，尽管鉴定因果遗传变异，更少地翻译来改善临床实践还没有到来。在过去的十年里，直接和间接的证据表明，活化的T细胞，特别是Th1表型在JRA的发病机制中发挥了作用。该项目的目标是确定编码T细胞调节分子的基因的遗传变异是否会导致JRA的易感性、发病机制和治疗结果的变化。这将通过两个具体目标来实现。1.分析参与T细胞调节的配体-受体对编码基因的遗传多样性。2.检测已鉴定的基因变异体与JRA的易感性和/或JRA的可变表达能力之间的关联和连锁。这些研究将使用3个不同的队列进行，这些队列代表了美国最大的JRA患者集合：(1)140对JRA同胞；(2)500名患有JRA及其父母的单身患者；以及(3)从居住在西部山区的650多名JRA患者登记中新确诊的病例。一项为期五年的指导计划被提出，该计划将包括教学和研究培训，并将由犹他大学的两名知名科学家指导。通过NIH资助的K30奖项，犹他大学普通临床研究中心提供了一个独特的临床研究教学培训计划，重点是人类疾病的遗传基础。该计划结合了对资源的访问，如多用户核心设施、大学大型研究中心和大学医院的指定单位，为成熟的临床研究人员提供具体的指导强化研究经验。因此，犹他大学为最大限度地发挥这项研究和申请人的潜力提供了一个理想的环境。

项目成果

Juvenile idiopathic arthritis and exposure to fine particulate air pollution.

• 发表时间: 2009-09
• 期刊: Clinical and experimental rheumatology
• 影响因子: 3.7
• 作者: Andrew S. Zeft;S. Prahalad;S. Lefèvre;B. Clifford;Bernadette McNally;J. Bohnsack;C. Pope

The genetics of juvenile idiopathic arthritis: what is new in 2010?

• DOI: 10.1007/s11926-010-0087-0
• 发表时间: 2010-04-01
• 期刊: Current rheumatology reports
• 影响因子: 5
• 作者: Angeles-Han, Sheila;Prahalad, Sampath
• 通讯作者: Prahalad, Sampath