Study of DMA and DMB as susceptibility genes of SLE, PSS and RA

DMA和DMB作为SLE、PSS和RA易感基因的研究

• 批准号: 09670470
• 负责人: TAKEUCHI Fujio
• 金额: $ 1.79万
• 依托单位: The University of Tokyo
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1997
• 资助国家: 日本
• 起止时间: 1997 至 1999
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09670470/
• 关键词: RA; SLE; PSS; DMA; DMB; HLA-DR; susceptibility gene; ethnics; 人種差; 肺繊維症; TNF; a-Scl-70; 抗DNA抗体; C4; 多型; 慢性関節リウマチ; HLADR; TAP; 蛋白尿

In this study, the possibilities were examined that DM genes worked as susceptibility genes of RA, PSS and SLE, and the relationships between DM and clinical features were examined. In normal control (n=77), DMA*0101-0103 and DMB*0101-0103 alleles were observed. A strong positive association was shown between DMA*0102 and DMB*00101. In Japanese, frequencies of DMA*0102 and DMB*0101 were decreased, and those of DMB*0102 and *0103 were increased comparing to Caucasians. The differences in distribution were obvious. In RA (n=91), a frequency of DMB*0101 (52.5%) was sligtly increased. An weak association was observed between DRB1*0405, which was known to be increased in RA, and DMB*0101 ( χィイD12ィエD1=3.02). This inducated that an increase in DMB*0101 in RA was secondary to an increase in DRB1*0405. As disease susceptibility haplotypes, DRBl*0405-[TAP2B-DMA*0102-DMB*0101] would work positively and DRB1*0802-DMB*0103 would work protectively. Examinations of relations to clinical features reve … More aled that a frequency of r-SS Aantibody was higher in DMB*0102 group. (27.3%) and a frequency of an antibody to Ezrin 80KD antigen (61.5% was higher in DMA*0102 group. Moreover, the positivity of proteinuria was higher in DMA*0102 group (44%). No association was observed between the rheumatoid factor and DM. In whole PSS group, a frequency of DMB*0103 was 20.0% and that was decreased comparing to control. The frequencies of DMB*0101 were 70.0% in diffuse scleroderma (DS) and 68.2% in the anti-Scl-70 positive group (Scl), and these frequencies were significantly higher. The significant association was observed between DMB*0101 and DRB1*1502, that was known to be increased in DS and Scl. These observation indicated that the increase in DMB*0101 would be secondary to the increase in DRB1*1502. As a disease susuceptibility haplotype. C4BQ0-DRB1*1502-DMB*0101 was proposed in DS and Scl. A significant negative association was observed between DMB*0103 and lung fibrosis in PSS. Examinations of TNF and HSP-70 showed no significant association to lung fibrosis. In SLE (n=51) no significant difference was observed in frequencies of DMA and DMB alleles comparing to those in control. A frequency of DMB*0101 was increased in the anti-DNA antibody positive group (p=0.045) and the frequency was also slightly higher in SS-A group. In this study, no nobel DM allele was observed. Less

本研究探讨了DM基因作为RA、PSS和SLE易感基因的可能性，以及DM与临床特征的关系。在正常对照组（n=77）中观察到DMA*0101-0103和DMB*0101-0103等位基因。DMA*0102和DMB*00101之间显示出强正相关。在日本人中，与高加索人相比，DMA*0102和DMB*0101的频率降低，DMB*0102和 *0103的频率升高。分布差异明显。在RA（n=91）中，DMB*0101（52.5%）的频率略有增加。在已知在RA中增加的DRB 1 *0405和DMB*0101之间观察到弱关联（χ 2 = D12，χ 2 = D1=3.02）。提示RA患者DMB*0101的升高继发于DRB 1 *0405的升高。DRB 1 *0405-[TAP 2B-DMA *0102-DMB*0101]作为疾病易感性单倍型可能起正向作用，DRB 1 *0802-DMB*0103作为疾病保护性单倍型可能起保护性作用。检查与临床特征的关系 ...更多信息 提示DMB*0102组r-SS A抗体阳性率较高。(27.3 DMA*0102组抗Ezrin 80 KD抗体阳性率（61.5%）高于DMA*0102组（P <0.01）。DMA*0102组蛋白尿阳性率为44%。类风湿因子和糖尿病之间没有观察到关联。在整个PSS组中，DMB*0103的频率为20.0%，与对照组相比降低。DMB*0101在弥漫性硬皮病（DS）中的频率为70.0%，在抗Scl-70阳性组（Scl）中的频率为68.2%，两组间差异有统计学意义（P <0.05）。在DMB*0101和DRB 1 *1502之间观察到显著关联，已知在DS和Scl中增加。这些观察结果表明，DMB*0101的增加继发于DRB 1 *1502的增加。作为疾病易感性单倍型。DS和Scl中提出了C4 BQ 0-DRB 1 *1502-DMB*0101。在PSS中观察到DMB*0103与肺纤维化之间的显著负相关。TNF和HSP-70的检查显示与肺纤维化无显著相关性。SLE组（n=51）DMA和DMB等位基因频率与对照组比较无显著性差异。抗DNA抗体阳性组DMB*0101的频率增加（p=0.045），SS-A组的频率也略高。在本研究中，没有观察到nobel DM等位基因。少

项目成果

Fujio Takeuchi, et al.: "Association of DM genes in systemic sclerosis is secondary to the association with HLA genes"Scand J Rheumatol. 26. 174-179 (1997)

Fujio Takeuchi 等人：“系统性硬化症中 DM 基因的关联继发于与 HLA 基因的关联”Scand J Rheumatol。

滝沢健司、竹内二士夫: "検査の進めかたと個々の疾患の診断、活動性の評価"Medical Practice. 15. 589-598 (1998)

Kenji Takizawa、Fushio Takeuchi：“如何进行个体疾病的测试、诊断和活动评估”医学实践 15. 589-598 (1998)。

Park MH, Takeuchi F et al.: "Association of HLA-DRB1 epitopes and alleles with rheumatoid arthritis in Koreans."Genetic diversity of HLA. II. 660-662 (1997)

Park MH、Takeuchi F 等人：“HLA-DRB1 表位和等位基因与韩国人类风湿性关节炎的关联。”HLA 的遗传多样性。

Wei T, Takeuchi F., et al.: "Detection of disease-specific augumentation of abnormal immunoglobuline G in sera of patients with rheumatoid arthritis."Glycoconjugate J. 15. 929-934 (1998)

Wei T、Takeuchi F. 等人：“检测类风湿性关节炎患者血清中异常免疫球蛋白 G 的疾病特异性增强。”Glycoconjugate J. 15. 929-934 (1998)

Fujio Takeuchi, et al.: "C4A and C4B null alleles are genetic markers of different types of systemic sclerosis in Japanese patients"Clin Exp Rheumatol. 16. 55-60 (1998)

Fujio Takeuchi 等人：“C4A 和 C4B 无效等位基因是日本患者不同类型系统性硬化症的遗传标记”Clin Exp Rheumatol。