Minority Predoctoral Fellowship Program

描述（由申请人提供）：本研究将通过描述不同种族之间类风湿性关节炎（RA）和幼年型类风湿性关节炎（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人中进行的，而美洲印第安人的RA和JRA患病率最高，并且更严重。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之间，本研究假设，细胞因子启动子多态性将被揭示为具有显着的遗传异质性之间的受影响的个人的美洲印第安人和高加索人。为了验证这一假设，本研究将使用夹心ELISA细胞因子阵列和mRNA微阵列来鉴定组间差异细胞因子表达。新的启动子多态性将通过高通量自动测序在影响细胞因子表达的转录结合位点中鉴定，并随后进行病例对照关联研究。将通过实时PCR和siRNA测定来验证这种新型多态性的差异表达。这项研究的结果将有助于更专业的诊断测试和治疗受影响的个人。

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.