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, Tsutomu Takeuchi, T. Hara

Research output: Contribution to journalArticle

119 Citations (Scopus)

Abstract

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
JournalRheumatology
Volume40
Issue number6
Publication statusPublished - 2001
Externally publishedYes

Fingerprint

Systemic Lupus Erythematosus
Alleles
Population
Genes
Exons
Linkage Disequilibrium
Autoantigens
3' Untranslated Regions
Genetic Promoter Regions
Autoantibodies
Introns
Pathology
T-Lymphocytes

Keywords

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

ASJC Scopus subject areas

  • Neuroscience(all)
  • Rheumatology

Cite this

Ahmed, S., Ihara, K., Kanemitsu, S., Nakashima, H., Otsuka, T., Tsuzaka, K., ... Hara, T. (2001). Association of CTLA-4 but not CD28 gene polymorphisms with systemic lupus erythematosus in the Japanese population. Rheumatology, 40(6), 662-667.

Association of CTLA-4 but not CD28 gene polymorphisms with systemic lupus erythematosus in the Japanese population. / Ahmed, S.; Ihara, K.; Kanemitsu, S.; Nakashima, H.; Otsuka, T.; Tsuzaka, K.; Takeuchi, Tsutomu; Hara, T.

In: Rheumatology, Vol. 40, No. 6, 2001, p. 662-667.

Research output: Contribution to journalArticle

Ahmed, S, Ihara, K, Kanemitsu, S, Nakashima, H, Otsuka, T, Tsuzaka, K, Takeuchi, T & Hara, T 2001, 'Association of CTLA-4 but not CD28 gene polymorphisms with systemic lupus erythematosus in the Japanese population', Rheumatology, vol. 40, no. 6, pp. 662-667.
Ahmed S, Ihara K, Kanemitsu S, Nakashima H, Otsuka T, Tsuzaka K et al. Association of CTLA-4 but not CD28 gene polymorphisms with systemic lupus erythematosus in the Japanese population. Rheumatology. 2001;40(6):662-667.
Ahmed, S. ; Ihara, K. ; Kanemitsu, S. ; Nakashima, H. ; Otsuka, T. ; Tsuzaka, K. ; Takeuchi, Tsutomu ; Hara, T. / Association of CTLA-4 but not CD28 gene polymorphisms with systemic lupus erythematosus in the Japanese population. In: Rheumatology. 2001 ; Vol. 40, No. 6. pp. 662-667.
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abstract = "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.",
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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, Tsutomu

AU - Hara, T.

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

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