Core 2

核心2

• 批准号: 8045897
• 负责人: LUCILA OHNO-MACHADO
• 金额: $ 41.97万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-09-20 至 2015-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8045897
• 关键词: Acute; Address; Adenovirus Infections; Adenoviruses; Affect; Age; Algorithms; Aneurysm; Automobile Driving; Bioinformatics; Biological; Calcineurin; Cardiovascular system; Child; Clinical; Clinical Data; Collaborations; Communicable Diseases; Complementary DNA; Complex; Coronary artery; DNA; Data; Data Analyses; Databases; Diagnostic tests; Disease; Disease susceptibility; Dose; Etiology; Face; Fever; Gene Expression; Genes; Genetic Transcription; Genetic Variation; Genotype; Heart Diseases; Immunologics; Individual; Infectious Agent; Inflammation; Institution; Intravenous Immunoglobulins; Laboratories; Lead; Life; Link; MicroRNAs; Mining; Molecular; Molecular Profiling; Mucocutaneous Lymph Node Syndrome; Online Systems; Outcome; Pathogenesis; Pathway interactions; Patients; Pattern; Phenotype; Play; RNA; Reaction; Research Personnel; Risk; Role; Sampling; Single Nucleotide Polymorphism; Software Engineering; Study models; Syndrome; System; Testing; United States National Institutes of Health; Variant; Vasculitis; Whole Blood; Work; cardiovascular risk factor; clinical phenotype; genetic variant; innovation; insight; model development; molecular phenotype; novel; prevent; repository; response; tool; treatment response; treatment strategy

Core 2 - Driving Biological Projects Three DBPs were selected for the initial 3 years, with primary collaborations representing geographically diverse institutions. These will be replaced in Year 4 by new DPBs, in which a wider array of institutions will be represented. B.1.DBP1 Molecular Phenotyping of Kawasaki Disease Kawasaki disease (KD) is a self-limited, acute vasculitis that is the most common cause of acquired heart disease in children. Coronary artery aneurysms occur in up to 25% of untreated children, but can be prevented by timely administration of high dose intravenous immune globulin (IVIG). While the etiology is unknown, an infectious agent that triggers an immunologic reaction in genetically susceptible hosts is suspected. Genotyping of haplotyped-tagged single nucleotide polymorphisms (SNPs) has identified genetic variation in the pathways for TGFp and calcineurin/NFAT that influence disease susceptibility and outcome. The biomedical researchers face a number of dilemmas: 1. There is no diagnostic test for the condition to aid in the recognition of affected children, and the clinical syndrome can mimic other, more common infectious diseases of children that do not require specific therapy. 2. Treatment with IVIG must be administered eariy in the course of the vasculitis to prevent permanent damage to the cardiovascular system. While most children will respond to IVIG, approximately 20-30% will have persistent or recrudescent fever and inflammation, will require additional therapy, and will be at increased risk of developing coronary artery abnormalities. 3. Tools need to be created to risk stratify patients and to convert molecular data into clinically useful phenotypes that can guide therapy.

核心2-驾驶生物项目 在最初的3年中，选择了三个DBP，主要合作代表了地理上不同的机构。新DPB将在第4年取代这些，其中将代表更广泛的机构。 B.1.DBP1川崎疾病的分子表型 川崎病（KD）是一种自限的急性血管炎，是儿童获得性心脏病的最常见原因。多达25％的未经治疗儿童发生冠状动脉动脉瘤，但可以及时给予高剂量的静脉静脉免疫球蛋白（IVIG）来预防。虽然病因尚不清楚，但怀疑会触发遗传易感宿主的免疫反应的传染剂。单倍分型标记的单核苷酸多态性（SNP）的基因分型鉴定了影响疾病易感性和结果的TGFP和钙调神经酶/NFAT途径中的遗传变异。生物医学研究人员面临许多困境： 1。没有诊断性测试来帮助识别受影响儿童的病情，临床综合征可以模仿其他不需要特定治疗的儿童的其他更常见的传染病。 2。在血管炎的过程中，必须对IVIG进行治疗，以防止对心血管系统的永久损害。尽管大多数儿童都会对IVIG做出反应，但大约20-30％的孩子会持续或重现发烧和炎症，需要额外的治疗，并且会增加患冠状动脉异常的风险。 3。需要创建工具以使患者分层并将分子数据转换为临床有用 可以指导治疗的表型。