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.
