TY - JOUR
T1 - Association of CTLA-4 but not CD28 gene polymorphisms with systemic lupus erythematosus in the Japanese population
AU - Ahmed, S.
AU - Ihara, K.
AU - Kanemitsu, S.
AU - Nakashima, H.
AU - Otsuka, T.
AU - Tsuzaka, K.
AU - Takeuchi, T.
AU - Hara, T.
N1 - Funding Information:
We extend special thanks to Yoko Katafuchi, Tamami Tanaka and Kanako Uchida for technical assistance. This work was supported by Grant-in-Aid for Scientific Research (B) from the Ministry of Health and Welfare and Ministry of Education, Science, and Culture of Japan.
PY - 2001
Y1 - 2001
N2 - Objective. Systemic lupus erythematosus (SLE) in a multisystem autoimmune disorder characterized by multiorgan pathology and autoantibodies against a variety of autoantigens. The CD28 and CTLA-4 genes might be candidate genes for SLE, because costimulation signals from CD80/CD86 to CD28/CTLA-4 have been suggested to play an important role in the activation or inactivation of T lymphocytes. Methods. We investigated three polymorphic regions within the CTLA-4 gene, a C/T base exchange in the promoter region - 318 (CTLA-4 - 318C/T), an A/G substitution in the exon 1 position 49 (CTLA-4 49A/G), an (AT)n repeat polymorphism in the 3′ untranslated region of exon 4 [CTLA-4 3′ (AT)n], and a CD28 gene polymorphism, a T/C substitution in the intron 3 position + 17 (CD28 IVS3 + 17T/C), in SLE patients and controls. Results. SLE patients had significantly higher frequencies of the CTLA-4 49G allele (P = 0.003) and of the CTLA-4 (AT)n 106 bp allele (P = 0.0008) than controls. We also found a strong linkage disequilibrium between the A allele of CTLA-4 49A/G and the 86 bp allele of CTLA-4 3′ (AT)n. On the contrary, no association was found between SLE and CTLA-4 -318C/T or CD28 IVS3 + 17T/C. Conclusion. We conclude that the CTLA-4 gene appears to play a significant role in the development of SLE in the Japanese population.
AB - Objective. Systemic lupus erythematosus (SLE) in a multisystem autoimmune disorder characterized by multiorgan pathology and autoantibodies against a variety of autoantigens. The CD28 and CTLA-4 genes might be candidate genes for SLE, because costimulation signals from CD80/CD86 to CD28/CTLA-4 have been suggested to play an important role in the activation or inactivation of T lymphocytes. Methods. We investigated three polymorphic regions within the CTLA-4 gene, a C/T base exchange in the promoter region - 318 (CTLA-4 - 318C/T), an A/G substitution in the exon 1 position 49 (CTLA-4 49A/G), an (AT)n repeat polymorphism in the 3′ untranslated region of exon 4 [CTLA-4 3′ (AT)n], and a CD28 gene polymorphism, a T/C substitution in the intron 3 position + 17 (CD28 IVS3 + 17T/C), in SLE patients and controls. Results. SLE patients had significantly higher frequencies of the CTLA-4 49G allele (P = 0.003) and of the CTLA-4 (AT)n 106 bp allele (P = 0.0008) than controls. We also found a strong linkage disequilibrium between the A allele of CTLA-4 49A/G and the 86 bp allele of CTLA-4 3′ (AT)n. On the contrary, no association was found between SLE and CTLA-4 -318C/T or CD28 IVS3 + 17T/C. Conclusion. We conclude that the CTLA-4 gene appears to play a significant role in the development of SLE in the Japanese population.
KW - CD28 gene
KW - CTLA-4 gene
KW - Polymorphism
KW - Systemic lupus erythematosus
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U2 - 10.1093/rheumatology/40.6.662
DO - 10.1093/rheumatology/40.6.662
M3 - Article
C2 - 11426024
AN - SCOPUS:0034935542
VL - 40
SP - 662
EP - 667
JO - Rheumatology (United Kingdom)
JF - Rheumatology (United Kingdom)
SN - 1462-0324
IS - 6
ER -