Minority Predoctoral Fellowship Program

少数族裔博士前奖学金计划

• 批准号: 8048340
• 负责人: SOPHIA Y CLELAND
• 金额: $ 2.78万
• 依托单位: GEORGE WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-07-02 至 2011-07-01
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8048340
• 关键词: Adult; Affect; Alleles; American Indians; Binding Sites; Biological Assay; Caucasians; Caucasoid Race; Child; Chronic Childhood Arthritis; Development; Diagnostic; Diagnostic tests; Disease; Enzyme-Linked Immunosorbent Assay; Epidemic; Ethnic group; Fellowship Program; Founder Effect; Gene Family; Genes; Genetic; Genetic Heterogeneity; Genetic Polymorphism; Genetic Transcription; Goals; High Prevalence; Immune; Immunity; Individual; Inflammatory Response; Medical; Medicine; Messenger RNA; Minority; Native Americans; Pathogenesis; Pathway interactions; Phenotype; Population; Predisposition; Rheumatoid Arthritis; Role; Severities; Severity of illness; Small Interfering RNA; Testing; Time; Tissue-Specific Gene Expression; Variant; adaptive immunity; base; case control; cytokine; health disparity; novel; pre-doctoral; promoter; response

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）：本研究将通过描述种族间类风湿性关节炎（RA）和幼年类风湿性关节炎（JRA）的遗传基础来消除健康差异。大多数关于 RA 和 JRA 的遗传学研究都是在白种人中进行的，而美洲印第安人的 RA 和 JRA 患病率最高，且形式更严重。由于疾病等位基因的显着遗传异质性已被证明存在于种族群体中，因此本研究假设细胞因子启动子多态性将被揭示在美洲印第安人和白种人的受影响个体之间具有显着的遗传异质性。为了检验这一假设，本研究将使用夹心 ELISA 细胞因子阵列和 mRNA 微阵列来识别组间细胞因子表达的差异。通过高通量自动测序，将在影响细胞因子表达的转录结合位点中鉴定新的启动子多态性，并进行病例对照关联研究。这些新型多态性的差异表达的验证将通过实时 PCR 和 siRNA 测定进行。这项研究的结果将有助于对受影响的个体进行更专业的诊断测试和治疗。