The Genetic and the Functional Study of DNA Repair System and the Susceptibility to Rheumatoid Arthritis.

Rheumatoid arthritis (RA) is a symmetric polyarticular arthritis that primarily affects the small diarthrodial joints of the hands and feet. In addition to inflammation in the synovium, which is the joint lining, the aggressive front of tissue called pannus invades and destroys local articular structures. The synovium is normally a relatively acellular structure with a delicate intimal lining. RA is also a chronic autoimmune disease and can lead to deformities and severe disabilities, due to irreversible damage of tendons, joints, and bones. It is known that RA can be considered as a complex genetic disease and many "disease-risk" genes or "disease-protective" genes can be involved. Numerous studies reported the association of IL-6, IL-8 genes with systemic lupus erythematosus (SLE) and the association of HLA-DR gene polymorphisms with RA. In addition, the chronic inflammatory process of RA is mediated through cytokines network, which leads to induce some destructive enzymes, like matrix metalloprotieases, in the cellular synovial tissue of joints. Although RA is a common arthritis with a prevalence of 1% in Taiwan, the pathogenesis is still incompletely studied, especially in DNA repair relative genes.

In this proposal, we would like to perform the following experiments:

1. Study the associations of the polymorphisms of DNA repair relative genes and the susceptibility to RA;
2. Study the associations of the copy number variation (CNV) of DNA repair relative genes and the susceptibility to RA;
3. Functional assay in DNA repair relative genes and compare it with the copy number variation (CNV), genotype and/or haplotype in RA patients; So far, we have analyzed the association between RA and several SNPs of MUTYH in DNA repair systems. We also analyzed the relationship between the SNPs results and RA using the pathological features. These data are helpful to clarify the susceptibility of RA patients with the genotype and/or haplotype in DNA repair system.

This study is valuable for the understanding the role of DNA repair system plays in the progression of rheumatoid arthritis and for the development of new therapeutic modality in the future.