Minority Predoctoral Fellowship Program

描述(由申请人提供)：这项研究将通过确定类风湿性关节炎(RA)和幼年类风湿性关节炎(JRA)在种族群体之间的遗传基础来消除健康差异。大多数关于RA和JRA的基因研究都是在高加索人中进行的，而美国印第安人的RA和JRA的患病率最高，也更严重。由于疾病等位基因的显著遗传异质性已被证明在种族之间存在，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高加索人受影响的个体之间具有显著的遗传异质性。为了验证这一假说，本研究将使用夹心ELISA细胞因子阵列和mRNA微阵列来鉴定不同组之间细胞因子的差异表达。通过高通量自动测序，将在影响细胞因子表达的转录结合部位识别新的启动子多态，并进行病例对照关联研究。将通过实时聚合酶链式反应和siRNA分析来验证这些新的多态的差异表达。这项研究的结果将有助于对受影响的个人进行更专门的诊断测试和治疗。

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.