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Abstract

Cytotoxic T lymphocyte associated antigen 4 (CTLA-4), a structural homologue of CD28, has been reported to be an important negative regulator of autoimmune diseases. Recent studies showed that CTLA-4 gene polymorphism was associated with several kinds of human autoimmune diseases, suggesting that CTLA-4 gene is probably a general susceptibility gene to autoimmune disease. The present study was conducted in Chinese to determine whether there is any association of the CTLA-4 gene polymorphism with the development of systemic lupus erythematosus (SLE). CTLA-4 gene polymorphism in promoter and exon 1 was detected by polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP) method in 81 patients with SLE and 81 normal controls. The results showed that there were no statistically significant differences in both exon 1 and promoter gene polymorphism between SLE patients and normal controls. The preliminary study does not suggest an association of the known polymorphism in exon 1 and promoter of CTLA-4 gene with Chinese SLE. However, SLE is a very heterogeneous syndrome and CTLA-4 gene polymorphism might correlate with some specific clinical features. To exploring this possibility, subgroup analysis in more patients needs to be performed.

Keywords

CTLA-4 gene exon 1 promoter

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References

Lenschow DJ , Walunas TL , Bluestone JA. CD28=B7 system of T cell costimulation . A Rev Immunol 1996; 14: 233-258 .

Harper K , Balzano C , Rouvier E et al. CTLA-4 and CD28 activated lymphocyte molecules are closely related in both mouse and human as to sequence, message expression, gene structure, and chromosomal location . J Immunol 1991; 147: 1037-1044 .

Krummel MF , Allison JP. CTLA-4 engagement inhibits IL-2 accumulation and cell cycle progression upon activation of resting T cells . J Exp Med 1996; 183: 2533-2540 .

Walunas TL , Bakker CY , Bluestone JA. CTLA-4 ligation blocks CD28-dependent T cell activation . J Exp Med 1996; 183: 2541-2550 .

Karandikar NJ , Vanderlugt CL , Walunas TL et al. CTLA-4: a negative regulator of autoimmune disease . J Exp Med 1996; 184: 783-788 .

Polymeropoulos MH , Xiao H , Rath DS et al. Dinucleotide repeat polymorphism at the human CTLA-4 gene . Nucleic Acids Res 1991; 19: 4018-4018 .

Larsen ZM , Kristiansen OP , Mato E et al. IDDM12 (CTLA-4) on 2q33 and IDDM13 on 2q34 in genetic susceptibility to type 1 diabetes . Autoimmunity 1999; 31: 35-42 .

Nistico L , Buzzetti R , Pritchard LE et al. The CTLA-4 gene region of chromosome 2q33 is linked to and associated with type 1 diabetes . Hum Mol Genet 1996; 5: 1075-1080 .

Deichmann K , Heinzmann A , Bruggenolte E et al. A Mse I RFLP in the human CTLA-4 promoter . Biochem Biophys Res Commun 1996; 225: 817-818 .

10.

Kristiansen OP , Larsen ZM , Pociot F . CTLA-4 in autoimmune diseases <Eth> a general susceptibility gene to autoimmunity? Genes Immun 2000; 1: 170-184 .

11.

Tan EM , Cohen AS , Fries JF , Masi AT et al. The 1982 revised criteria for the classification of systemic lupus erythematosus . Arthrit Rheum 1982; 25: 1271-1277 .

12.

Liu MF , Liu HS , Wang CR et al. Expression of CTLA-4 molecule in peripheral blood T lymphocytes from patients with systemic lupus erythematosus . J Clin Immunol 1998; 18: 392-398 .

13.

Concannon P , Golgin-Ewens KJ , Hinds DA et al. A second-generation screen of the human genome for susceptibility to insulin-dependent diabetes mellitus . Nature Genet 1998; 19: 2292-2296 .

14.

Gaffney PM , Kearns GM , Shark KB et al. A genome-wide search for susceptibility genes in human systemic lupus erythematosus sib-pair families . Proc Natl Acad Sci USA 1998; 95: 14875-14879 .

15.

Heward JM , Gordon C , Allahabadia A et al. The A-G polymorphism in exon 1 of the CTLA-4 gene is not associated with systemic lupus erythematosus . Ann Rheum Dis 1999; 58: 193-195 .

16.

Mehrian R , Quismorio FP , Strassmann G et al. Synergistic effect between IL-10 and bcl-2 genotypes in determining susceptibility to systemic lupus erythematosus . Arthrit Rheum 1998; 41: 596-602 .

17.

Pullmann R Jr , Lukac J , Skerenova M et al. CTLA-4 dimorphism in patients with systemic lupus erythematosus . Clin Exp Rheumatol 1999; 17: 725-729 .

18.

Barnes R , Grabs R , Polychronakos C. A CTLA-4 polymorphism affects lymphocyte mRNA levels but not associated with type 1 DM in a Canadian dataset . Diabetologia 1997; 40: 194-194 .

19.

Kouki T , Sawai Y , Gardine CA et al. CTLA-4 gene polymorphism at position 49 in exon 1 reduces the inhibitory function of CTLA-4 and contributes to the pathogenesis of Graves' disease . J Immunol 2000; 165: 6606-6611 .

CTLA-4 gene polymorphism in promoter and exon-1 regions in Chinese patients with systemic lupus erythematosus

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