한국인에서 류마토이드 관절염과 제 2 형 조직적합항원과의 연관성에 관한 연구 = Association between Class 2 MHC Antigen and Rheumatoid Arthritis in Koreans
Rheumatoid arthritis is a chronic inflammatory disease characterized as destructive polyarthritis and has evidence of immunogenetic and environmental elements in its etiologic factors. Many studies document that one of the key genetic elements is closely linked to the class II major histocompatibility complex located in chromosome 6. Although it is not. known precisely how HLA genes contribute to disease susceptibility, many studies document a close association between rheumatoid arthritis and the specific histocompatibility marker, HLA-DR4. However, studies of HLA-DR4 in disease severity have yielded conflictiing results. Association between HLA- DR4 and the rheumatoid factor, earlier age of onset, increased general disease severity and more erosive radiographic changes have been reported, but these associations have not been confirmed in other studies. In addition, there has been no report regarding the association between rheumatoid arthritis and class II MHC in Koreans. Therefore this is the first epidemiologic study regarding the association between rheumatoid arthritis and class II MHC. The disrtibution of class II major histocompatibility complex and association between HLA- DR4 and disease severity were analyzed in 206 Korean patients with rheumatoid arthritis in this study. The results were as follows: 1) HLA-DR4 was associated with rheumatoid arthritis in 61.6% of the patients studied. The relative risk and etiologic fraction of HLA-DR4 were 2.47 and 0.367, respectively. HLA-DR1 was positive in 11.1% and the etiologic fraction of HLA-DR1 was 0.008. Therefore HLA-DR4 was associated strongly with rheumatoid arthritis in Koreans, similar to other ethnic populations, but HLA-DR1 was not associated with rheumatoid arthritis in Koreans. 2) HLA-DR2 was positive in 19.9% and the preventive fraction of HLA-DR2 was 0.205. HLA-DR7 was positive in 4.3% and the preventive fraction of HLA- DR7 was 0.011. Hence HLA-DR2 was the most preventive class II MHC against the development of rheumatoid arthritis in this study. 3) HLA-Dgw3 was positive in 62.1% and the relative risk of HLA-DQw3 was 1.65, HLA-DQw7, which was known as HLA-DQw3.1, was positive in 20.5% and HLA-DR4 Dgw7 haplotype was positive in 15% of the total number of patients. 4) HLA-DR4 was significantly associated with a more advanced ARA anatomical grade and more severe radiographic changes, including bony erosion, joint space, narrowing and total radiographic score. 5) The rheumatoid facor was positive in 84.3% of the HLA-DR4 positive patients and positive in 82.3% of the HLA-DR4 negative patients. HLA-DR4 v as positive in 62.2% of the 172 seropositive patients and positive in 58.8% of the 34 seronegative patients. Therefore HLA-DR4 was not associated significantly with the presence of a rheumatoid factor in this study. 6) HLA-DR4 was not associated significantly with joint count (Ritchie index), ARA functional class, ESR, C-reactive protein or other demographic data. HLA-DR4 was not associated significantly with the positive rate of ANA, cryoglobulin. 7) Homozygous HLA-DR4 patients were 31 out of 127 DR4-positive patients and showed more advanced ARA anatomical stage and radiographic changes than heterozygous DR4 patients, but the difference was statistically insignificant. In summary, HLA-DR4 was significantly associated with rheumatoid arthritis in Koreans, similar to other ethnic populations, Also HLA-DR4 was significantly associated with more destructive arthritis, but not associated with rheumatoid factor positivity and the parameters representing disease activity of rheumatoid arthritis.더보기
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