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Association of CTLA‐4 but not CD28 gene polymorphisms with systemic lupus erythematosus in the Japanese population

2001; Oxford University Press; Volume: 40; Issue: 6 Linguagem: Inglês

10.1093/rheumatology/40.6.662

1462-0332

S. Ahmed, Kenji Ihara, Shigeru Kanemitsu, Hitoshi Nakashima, T Otsuka, Kensei Tsuzaka, Tsutomu Takeuchi, Toshiro Hara,

Immune Cell Function and Interaction

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.