Minority Predoctoral Fellowship Program

少数族裔博士前奖学金计划

• 批准号: 7387924
• 负责人: SOPHIA Y CLELAND
• 金额: $ 1.71万
• 依托单位: GEORGE WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-07-02 至 2010-07-01
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7387924
• 关键词: Native Americans; blood tests; caucasian American; clinical research; cytokine; enzyme linked immunosorbent assay; family genetics; gene expression; genetic polymorphism; genetic promoter element; genetic screening; genetic susceptibility; health disparity; health services research tag; high throughput technology; human genetic material tag; human subject; juvenile rheumatoid arthritis; microarray technology; polymerase chain reaction; predoctoral investigator; racial /ethnic difference; rheumatoid arthritis; small interfering RNA; tumor necrosis factor alpha

DESCRIPTION (provided by applicant): This study will eliminate health disparities by characterizing the genetic bases for rheumatoid arthritis (RA) and juvenile rheumatoid arthritis (JRA) between ethnic groups. Most genetic studies on RA and JRA have been in Caucasians while American Indians have the highest prevalence rates of and more severe forms of RA and JRA. Because significant genetic heterogeneity in disease alleles has been shown to exist among ethnic groups, this study hypothesizes that cytokine promoter polymorphisms will be revealed to have significant genetic heterogeneity between affected individuals of American Indians and Caucasians. To test this hypothesis, this study will use sandwich ELISA cytokine arrays and mRNA microarray to identify differential cytokine expression between groups. Novel promoter polymorphisms will be identified in transcription binding sites that affect cytokine expression via high-throughput automated sequencing, and followed through with case-control association studies. Verification of the differential expression of such novel polymorphisms will be executed via real-time PCR and siRNA assays. The results of this study will aid in more specialized diagnostic tests and treatment of affected individuals.

描述（由申请人提供）：这项研究将通过表征类风湿关节炎（RA）和少年类风湿关节炎（JRA）之间的遗传基础来消除健康差异。关于RA和JRA的大多数遗传研究都在高加索人，而美国印第安人的患病率最高，RA和JRA的形式更为严重。由于已经证明在族裔群体中存在疾病等位基因的显着遗传异质性，因此这项研究假设细胞因子启动子多态性将被发现在美国印第安人和高加索人受影响的个体之间具有显着的遗传异质性。为了检验这一假设，本研究将使用三明治ELISA细胞因子阵列和mRNA微阵列来鉴定组之间的差异细胞因子表达。新型启动子多态性将在通过高通量自动测序影响细胞因子表达的转录结合位点中鉴定出来，然后进行病例对照关联研究。将通过实时PCR和siRNA分析执行这种新型多态性的差异表达的验证。这项研究的结果将有助于进行更专业的诊断测试和对患者的治疗。