ab2006

Association of CTLA-4 with systemic sclerosis in Japanese patients

F. Takeuchi¹, K. Kawasugi¹, H. Nabeta¹, M. Mori¹, K. Tanimoto^1,2

¹Department of Internal Medicine, Faculty of Medicine, University of Tokyo, Tokyo; ²Health Service Center, University of Saitama, Urawa, Saitama, Japan.

ABSTRACT
Objective
The contribution of CTLA-4 alleles to the pathogenesis of systemic sclerosis (SSc) was studied in Japanese patients.

Methods
CTLA-4 typing in 2 dimorphic sites, +49 A/G and -308C/T, was carried out in 62 SSc patients and 107 normal subjects by the PCR- RFLP (restriction fragment length polymorphism) method. HLA-DRB1*15 and *08 genotyping were carried out by the PCR-SSCP (simple-stranded DNA conformation polymorphism) method.

Results
In SSc the frequency of the +49A allele increased slightly (40.3%), but was not significant. In SSc with diffuse scleroderma and SSc with anti-topoisomerase I antibody, the +49A also increased (43.8%, and 48.0%, respectively) but again was not significant. A significant increase in the +49A was not observed in SSc with HLA-DRB1*1502 or ORB1*0802. In contrast, the +49A had significantly increased in SSc with the anti-RNP antibody [52.9%, p = 0.0337, Odds ratio (OR) = 2.27 (95% confidential interval (CI) = 1.09 - 4.71)]. HLA-DRB1*1502 and *0802 had no influence on the association of anti-RNP antibody with the +49A. The +49AA genotype increased significantly in SSc without lung fibrosis [31.8%, p = 0.0456, OR = 3.37 (CI = 1.16 - 9.87)], especially in limited SSc without lung fibrosis [33.3%, p = 0.0319, OR = 3.62 (CI = 1.16 - 11.29)]. The dimorphism at -308 did not associate with SSc.

Conclusion
In Japanese scleroderma, the +49A allele of CTLA-4 increased in the presence of SSc with the anti-RNP antibody.

Key words
CTLA-4, RNP, SSc, lung fibrosis, Japanese.

This study was supported by grants from Ministry of Education, Culture, Sport, Science and Technology of Japan, and The Manabe Foundation.
Please address correspondence and reprint requests to: Fujio Takeuchi, MD, 504 Laboratory, Department of Internal Medicine (Allergy and Rheumatology), Faculty of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan. E-mail: fujio-tky@umin.ac.jp