Association of CTLA-4 with systemic sclerosis in Japanese patients

• Published in: Clinical and experimental rheumatology Vol. 20; no. 6; p. 823
• Main Authors: Takeuchi, F, Kawasugi, K, Nabeta, H, Mori, M, Tanimoto, K
• Format: Journal Article
• Language: English
• Published: Italy 01.11.2002
• Subjects: Abatacept; Antigens, CD; Antigens, Differentiation - genetics; CTLA-4 Antigen; DNA - analysis; Female; Gene Frequency; Genetic Predisposition to Disease; Genotype; HLA-DR Antigens - genetics; HLA-DRB1 Chains; Humans; Immunoconjugates; Japan; Male; Middle Aged; Odds Ratio; Polymerase Chain Reaction; Polymorphism, Restriction Fragment Length; Polymorphism, Single-Stranded Conformational; Pulmonary Fibrosis - complications; Pulmonary Fibrosis - ethnology; Pulmonary Fibrosis - genetics; Scleroderma, Systemic - complications; Scleroderma, Systemic - ethnology; Scleroderma, Systemic - genetics; Japan
• ISSN: 0392-856X

The contribution of CTLA-4 alleles to the pathogenesis of systemic sclerosis (SSc) was studied in Japanese patients. CTLA-4 typing in 2 dimorphic sites, +49 A/G and -308 C/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. 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. In Japanese scleroderma, the +49A allele of CTLA-4 increased in the presence of SSc with the anti-RNP antibody.