Rheumatology 2001; 40: 662-667
© 2001 British Society for Rheumatology
Original Papers |
Association of CTLA-4 but not CD28 gene polymorphisms with systemic lupus erythematosus in the Japanese population
Departments of Pediatrics and
1 Medicine and Biosystemic Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, and
2 Department of Internal Medicine II, Saitama Medical Center, Saitama, Japan
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.
KEY WORDS: CTLA-4 gene, CD28 gene, Polymorphism, Systemic lupus erythematosus.
Correspondence to: K. Ihara, Department of Pediatrics, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  B. Greve, L. Vijayakrishnan, A. Kubal, R. A. Sobel, L. B. Peterson, L. S. Wicker, and V. K. Kuchroo The Diabetes Susceptibility Locus Idd5.1 on Mouse Chromosome 1 Regulates ICOS Expression and Modulates Murine Experimental Autoimmune Encephalomyelitis J. Immunol., July 1, 2004; 173(1): 157 - 163. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M Hirashima, T Fukazawa, K Abe, Y Morita, M Kusaoi, and H Hashimoto Expression and activity analyses of CTLA4 in peripheral blood lymphocytes in systemic lupus erythematosus patients Lupus, January 1, 2004; 13(1): 24 - 31. [Abstract] [PDF]
|
|