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

S. Ahmed, K. Ihara, S. Kanemitsu, H. Nakashima, T. Otsuka, K. Tsuzaka, T. Takeuchi, T. Hara

Research output: Contribution to journalArticlepeer-review

136 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)662-667
Number of pages6
Issue number6
Publication statusPublished - 2001
Externally publishedYes


  • CD28 gene
  • CTLA-4 gene
  • Polymorphism
  • Systemic lupus erythematosus

ASJC Scopus subject areas

  • Rheumatology
  • Pharmacology (medical)


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