頁籤選單縮合
題 名 | Rheumatoid Arthritis: An Orchestra of Genetic, Autoimmune and Environmental Factors |
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作 者 | Tan, Wenfeng; Hung, Weiting; Tsao, Betty P.; | 書刊名 | Adaptive Medicine |
卷 期 | 3:2 2011.10[民100.10] |
頁 次 | 頁73-84 |
分類號 | 415.695 |
關鍵詞 | Genetic epidemiology; GWAS; Autoimmune; Smoking; Periodontal disease; Rheumatoid arthritis; |
語 文 | 英文(English) |
英文摘要 | Clinical presentation of rheumatoid arthritis (RA) may be the results of a combination of genetic and environmental risk factors resulting in a prominent autoimmune component. Evidence from case-control studies, either using the candidate gene or genome-wide association approaches, have revealed more than 30 loci that are associated with RA susceptibility. Many RA-associated gene variants are involved in pathways of T-cell, B-cell and NF-κB signaling. HLA-DRB1 shared epitope is a major determinant of genetic predisposition to RA development in different ethnic groups, which is involved in T-cell antigen presentation and the production of anti-cyclic citrullinated peptides antibodies (ACPA). The presence or absence of ACPA appears to stratify RA patients into two distinct subsets with different genetic profiles, clinical courses and histological findings. In addition to the shared epitope, a growing number of gene variants is associated with RA in multiple ethnic groups, including STAT4, AFF3, CCR6, CCL21, and BLK. Some of the RA-associated gene variants may be particularly important in a specific ethnic group; for example, PTPN22 in populations of European ancestry and PADI4 in Asians. Emerging evidence has shown that many disease-associated loci are shared among multiple autoimmune diseases, including type 1 diabetes, systemic lupus erythematosus, inflammatory bowel disease and multiple sclerosis, suggesting the presence of common pathways in the pathophysiology of these diseases. In addition to genetic risk factors, recent data have implicated cigarette smoking and infection of P. ginivitis as environmental risk factors that may potentiate disease risk in genetically susceptible individuals. Frequent and long-term exposure to insecticides also may increase risks for RA development. Further studies to understand functional consequences of disease-associated gene variants and gene-environment interactions that impact on the immune system are likely to lead to the development of novel therapies and/or prevention strategies for RA. |
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