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Genetic contribution of MHC class II and III genes to pathogenesis of RA and PSS.

MHC II 类和 III 类基因对 RA 和 PSS 发病机制的遗传贡献。

基本信息

批准号：
05670416
负责人：
TAKEUCHI Fujio
金额：
$ 1.34万
依托单位：
Tokyo University
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1993
资助国家：
日本
起止时间：
1993 至 1994
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-05670416/
关键词：
rheumatoid arthritis HLA-DR C4 TNF HSP-70 PSS genotype susceptible genes genctype TNF-α Hsp-70

项目摘要

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 … More 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

建立了人类白细胞抗原DR基因分型的SSCP方法。类风湿性关节炎患者DRB1*0405基因显著增加，DRB1*0401基因也有增加，但未见*0101。DRB1*0802基因表达显著降低，被认为是一个抑制基因。对肿瘤坏死因子和热休克蛋白-70的RFLP分析表明，在肿瘤坏死因子-热休克蛋白-70区域可能存在新的RA易感基因。对人类白细胞抗原B67和肿瘤坏死因子10.0的关联分析表明，致病基因不是C4AQ0本身，而是C4AQ0附近的一个易感基因。在临床表现方面，TNF10.0、HSP9.0和DRB1*0405的表达与尿蛋白升高、C4和CH50降低有关。未观察到与疾病活动性相关。此外，还发现HSP9.0kb和*0405与SSA构象抗体有关。还观察到TNF5.5(-)与未知的ANA相关。在朝鲜族类风湿关节炎中，*0405和*0401也有显著增加。未观察到DR1的增加。DRB1*0802为肌萎缩侧索硬化症…更多的o下降，如日本所示。DQ分子上的氨基酸序列“RKRAA”没有关联。来自日本和韩国的结果表明，DR4的完整构象以及QRRAA序列的重要性。在PSS中，DRB1*1502-DRB5*0102单倍型和DRB1*0802在弥漫性硬皮病和/或抗Sc170阳性硬皮病中增加。67-71位氨基酸定位与DRB1*1101和*1104相似，据报道，DRB1*1101和*1104在高加索PSS中增加，可能是易感序列。弥漫性硬皮病和a-scl-70阳性硬皮病的肿瘤坏死因子5.5条带明显减少(27.3%和23.5%)。5.5波段与*1502呈显著负相关。与C4AQ0呈正相关，与C4BQ0呈显著负相关。HSP8.5kb条带与抗着丝粒抗体呈负相关。DQ6.1基因在弥漫性硬皮病(59%)和a-scl-70阳性硬皮病(52.4%)中均有表达。我们的观察部分阐明了RA和PSS中MHC的遗传因素，我们认为有必要对遗传因素的各个方面进行研究，以阐明胶原病的发病机制，开发临床有效的治疗方法。较少