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。

C4A and C4B null alleles are genetic markers of different types of systemic sclerosis in Japanese patients.

作者信息

Takeuchi F, Nabeta H, Hong G H, Matsuta K, Tokunaga K, Tanimoto K, Nakano K

机构信息

Dept. of Medicine and Physical Therapy, Faculty of Medicine, University of Tokyo, Japan.

出版信息

Clin Exp Rheumatol. 1998 Jan-Feb;16(1):55-60.

PMID:9543562

Abstract

OBJECTIVE

The contribution of the polymorphism of complement C4A and C4B alleles to the pathogenesis of systemic sclerosis (SSc) was studied in Japanese patients.

METHODS

C4A and C4B typing was carried out in 44 SSc patients and in 83 normal subjects using electrophoresis followed by immunofixation and immunoblotting. HLA-DR typing and HLA DRB1*15 and *08 genotyping were carried out by the PCR method and the PCR-SSCP method, respectively.

RESULTS

In SSc with diffuse scleroderma, the frequency of C4BQ0 was significantly increased (44.4%, p < 0.001, pc < 0.01). In SSc with antitopoisomerase I antibody (a-Scl-70) C4BQ0 was also increased (50.0%, p < 0.001, pc < 0.01). Association analysis indicated that the increase in C4BQ0 was not primary but reflected an increase in HLA-DRB1*1502. In contrast, C4A/Q0 was significantly increased in limited scleroderma (53.8%, p < 0.005, pc < 0.05) and SSc without a-SCL-70 (53.8%, p < 0.005, pc < 0.05).

CONCLUSION

Diffuse scleroderma with SSC with a-Scl-70 have different genetical backgrounds from limited scleroderma and SSc without a-Scl-70, respectively, in Japanese patients. C4AQ0 were independent genetic markers for each clinical subgroup and for a a-Scl-70 positivity.

摘要

目的

在日本患者中研究补体C4A和C4B等位基因多态性对系统性硬化症（SSc）发病机制的影响。

方法

采用电泳继以免疫固定和免疫印迹法对44例SSc患者和83名正常受试者进行C4A和C4B分型。分别采用聚合酶链反应（PCR）法和PCR-单链构象多态性（SSCP）法进行HLA-DR分型以及HLA DRB115和08基因分型。

结果

在弥漫性硬皮病型SSc中，C4BQ0频率显著升高（44.4%，p<0.001，校正p<0.01）。在抗拓扑异构酶I抗体（抗Scl-70）阳性的SSc中，C4BQ0也升高（50.0%，p<0.001，校正p<0.01）。关联分析表明，C4BQ0的升高并非原发性的，而是反映了HLA-DRB1*1502的增加。相比之下，C4A/Q0在局限性硬皮病（53.8%，p<0.005，校正p<0.05）和无抗SCL-70的SSc（53.8%，p<0.005，校正p<0.05）中显著升高。