Association of CTLA-4 with systemic sclerosis in Japanese patients.
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 -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.


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.


CONCLUSIONS
In Japanese scleroderma, the +49A allele of CTLA-4 increased in the presence of SSc with the anti-RNP antibody.
Takeuchi
F
F
Department of Internal Medicine, Faculty of Medicine, University of Tokyo, Tokyo, Japan. fujio-tky@umin.ac.jp
Kawasugi
K
K
Nabeta
H
H
Mori
M
M
Tanimoto
K
K
D000069594:Abatacept; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000235:genetics*; D060908:CTLA-4 Antigen; D004247:DNA / Q000032:analysis; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006684:HLA-DR Antigens / Q000235:genetics; D059811:HLA-DRB1 Chains; D006801:Humans; D018796:Immunoconjugates; D007564:Japan; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D018807:Polymorphism, Single-Stranded Conformational; D011658:Pulmonary Fibrosis / Q000150:complications / Q000208:ethnology / Q000235:genetics; D012595:Scleroderma, Systemic / Q000150:complications / Q000208:ethnology / Q000235:genetics*
D015703:Antigens, CD; D000943:Antigens, Differentiation; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; D018796:Immunoconjugates; D000069594:Abatacept; D004247:DNA