Genetic contribution of MHC class II and III genes to pathogenesis of RA and PSS.
| Project/Area Number |
05670416
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
内科学一般
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| Research Institution | Tokyo University |
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Principal Investigator |
TAKEUCHI Fujio Tokyo University, Dep.of Medicine, Assistant Professer, 医学部(病), 講師 (70154979)
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| Co-Investigator(Kenkyū-buntansha) |
TOKUNAGA Katsushi Japan Red Cross, Dep.of 1st Reserch, Chief, 研究一課, 課長 (40163977)
NAKANO Keiichiro Tokyo University, Dep.of Medicine, Medical Doctor, 医学部(病), 助手 (10090490)
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| Project Period (FY) |
1993 – 1994
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| Project Status |
Completed (Fiscal Year 1994)
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| Budget Amount *help |
¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1994: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1993: ¥1,200,000 (Direct Cost: ¥1,200,000)
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| Keywords | rheumatoid arthritis / HLA-DR / C4 / TNF / HSP-70 / PSS / genotype / susceptible genes / genctype / TNF-α / Hsp-70 |
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| Research Abstract |
SSCP method for genotyping HLA DR was estabilished. In RA significant increase in DRB1*0405 was observed and increase in DRB1*0401 was also shown but not *0101. DRB1*0802 was decreased significantly and was thought to be an suppressive gene. RFLP analysis of TNF and HSP-70 suggested a possibility of new RA susceptible gene in the region of TNF-HSP-70. An analysis of the association with HLA-B67 and TNF10.0 suggested that not C4AQ0 itself but a susceptible gene near the C4AQ0 would contributed to the disease. In the aspect of clinical features, assosiation of TNF10.0, HSP9.0 and DRB1*0405 with an increase in urine protein, and a decrease of C4 and CH50. No assosiation was observed with disease activity. Additionally, an association of HSP9.0kb and *0405 with conformational antibody of SSA was suggested. An association of TNF5.5 (-) with unknown ANA was also observed. In Korean RA,a significant increase in *0405 and *0401 was also shown. No increase in DR1 was observed. DRB1*0802 was als
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o decreased as was shown in Japanease. The amino acid sequence "RKRAA" on DQ molecule was not associated. The result from Japanese and Korean indicated the importance of whole conformation of DR4 as well as QRRAA sequence. In PSS,increases in DRB1*1502-DRB5*0102 haplotype and DRB1*0802 were observed in diffuse scleroderma and/or anti-Sc170 positive scleroderma. Amino acids positioning at 67-71 are similar to those of DRB1*1101 and *1104 which are reported to be increased in caucasion PSS and are assumed to be susceptible sequence. TNF 5.5 band was significantly decreased in diffuse scleroderma and a-Scl-70 positive screloderma (27.3% and 23.5% respectively). The 5.5 band show significant correlation negatively with *1502. The band also show positive association with C4AQ0 and significant negative assosiation with C4BQ0. Moreover HSP 8.5 kb band show associated with anti-centromere antibody negatively. In HLA-DQ typing, DQ6.1 was increased in diffuse scleroderma (59%) and a-Scl-70 positive scleroderma (52.4%). Our observation partialy clarified the genetic factor of MHC in RA and PSS.We think it is necessary to study the various aspects of genetic factors for clarifing the pathogenesis of collagen disease and developing the clinicaly available therapy. Less
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Report
(3 results)
Research Products
(17 results)
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[Publications] Tsuchiya N,Endo T,Matsuta K,Yoshinoya S,Takeuchi F,Nagano Y,Shiota M,Fuyukawa K,Kochibe N,Ito K,Kobata A: "Detection of glycosylation abnormelity in rheunmatoid IgG using N-acetyl glucosamine-specific psathyvella velutina lectin." J Immunol. 151. 1137-1146 (1993)
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「研究成果報告書概要(欧文)」より
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