中国人CTLA-4基因-1722位点多态性与系统性红斑狼疮的相关性

南方医科大学学报 ›› 2004, Vol. 24 ›› Issue (10): 1107-1112.

中国人CTLA-4基因-1722位点多态性与系统性红斑狼疮的相关性

徐安平¹, 尹培达², 苏晓燕¹

1. 中山大学附属第二医院肾内科, 广东, 广州, 510120;
2. 中山大学附属第一医院肾内科, 广东, 广州, 510120

出版日期:2004-10-20 发布日期:2004-10-20
基金资助:
收稿日期:2004-6-8。
基金项目:广州市科技计划项目(2001-Z-129-02)
作者简介:徐安平,男,副主任医师,电话:020-81332487,E-mail:Anpxu_gzb@21cn.net

Association of CTLA-4 promoter -1722 polymorphism with systemic lupus erythematosus in Chinese

XU An-ping¹, YIN Pei-da², SU Xiao-yan¹

1. 中山大学附属第二医院肾内科, 广东, 广州, 510120;
2. 中山大学附属第一医院肾内科, 广东, 广州, 510120

Online:2004-10-20 Published:2004-10-20

摘要/Abstract

摘要： 目的研究细胞毒性T淋巴细胞相关抗原4(cytotoxic Tlymphocyte-associated antigen 4,CTLA-4)基因启动子区-1722位点(T/C)多态性在中国南方地区汉族人群中的分布及其与系统性红斑狼疮(SLE)的相关性。方法 103例患者诊断均符合1982年美国风湿病学会修订的SLE分类标准,其中男13例,女90例。正常对照组110例,其中男21例,女89例。全部研究对象均为无血缘关系的中国南方汉族人群。采用微量全血提取法,从EDTA抗凝血中提取DNA。应用聚合酶链反应(PCR)-限制性片段长度多态性(RFLP)方法,对所有SLE患者和正常对照者进行CTLA-4基因-1722位点多态性检测。结果 CTLA-4基因-1722位点多态性在中国南方地区人群中普遍存在,与正常对照组比较,SLE患者CTLA-4基因-1722位点TC基因型频率明显升高(42%vs58%,P<0.05),CC基因型频率明显降低(25%vs15%,P<0.05),TT基因型频率虽有降低趋势,但差异无显著性(33%vs27%,P>0.05);而SLE患者等位基因频率和携带者频率分布均无显著性差异(P>0.05)。在不同人种CTLA-4基因-1722位点基因型频率和等位基因频率分布存在差异。结论 CTLA-4基因-1722位点多态性与SLE明显相关,CTLA-4基因可能是SLE的易感基因。

Abstract: Objective To investigate the possible association of cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) promoter -1722 polymorphism with systemic lupus erythematosus (SLE) in the population in southern China.Methods A total of 103 SLE patients (13 males and 90 females with an average age of 33.63±12.58 years) diagnosed according to the SLE diagnostic criteria of the American College of Rheumatology revised in 1982 and 110 healthy ethnically matched controls (21 males and 89 females with an average age of 27.49±8.60 years),all from southern China,were enrolled in the study. DNA was extracted from EDTA-treated blood samples according to the standard isolation procedure. The restriction fragment length polymorphism-polymerase chain reaction was used to analyze CTLA-4 promoter-1722 polymorphism in SLE patients and healthy controls. Results Compared with the controls,the SLE patients had higher frequencies of TC genotype (42%vs58%,P<0.05) and lower frequency of CC genotype (25%vs15%,P<0.05). There were no significant differences in the frequencies of TT genotype,alleles and phenotypes between SLE patients and controls; however,significant differences in the frequencies of TT genotype and alleles of CTLA-4 promoter -1722 were found among different races (P<0.05).Conclusion CTLA-4 promoter -1722 polymorphism appears to be associated with SLE susceptibility in southern Chinese population.

中图分类号:

R593.241

徐安平¹, 尹培达², 苏晓燕¹. 中国人CTLA-4基因-1722位点多态性与系统性红斑狼疮的相关性[J]. 南方医科大学学报, 2004, 24(10): 1107-1112.

XU An-ping¹, YIN Pei-da², SU Xiao-yan¹. Association of CTLA-4 promoter -1722 polymorphism with systemic lupus erythematosus in Chinese[J]. Journal of Southern Medical University, 2004, 24(10): 1107-1112.

参考文献

[1] Greenwald RJ,Latchman YE,Sharpe AH.Negative co-receptors on lymphocytes [J].Curr Opin Immunol,2002,14(3):391-6.
[2] Salomon B,Bluestone JA.Complexities of CD28/B7:CTLA-4costimulatory pathways in autoimmunity and transplantation [J].Annu Rev Immunol,2001,19(2):225-52.
[3] Eagar TN,Karandikar NJ,Bluestone JA,et al.The role of CTLA-4in induction and maintenance of peripheral T cell tolerance[J].Eur J Immunol,2002,32(4):972-81.
[4] Johnson GC,Esposito L,Barratt BJ,et al.Haplotype tagging for the identification of common disease genes[J].Nat Genet,2001,29(2):233-7.
[5] Kristiansen OP,Larsen ZM,Pociot F.CTLA-4 in autoimmune diseases-a general susceptibility gene to autoimmunity [J] ? Genes Immun,2000,1(3):170-84.
[6] Barton A,Jury F,Eyre S,et al.Haplotype analysis in simplex families and novel analytic approaches in a case-control cohort reveal no evidence of association of the CTLA-4 gene with rheumatoid arthritis[J].Arthritis Rheum,2004,50(3):748-52.
[7] Hudson LL,Rocca K,Song YW,et al.CTLA-4 gene polymorphisms in systemic lupus erythematosus:a highly significant association with a determinant in the promoter region[J].Hum Genet,2002,111(4-5):452-5.
[8] Bouqbis L,Izaabel H,Akhayat O,et al.Association of the CTLA-4promoter region (-1661G allele) with type 1 diabetes in the South Moroccan population [J].Genes Immun,2003,4(2):132-7.
[9] Hudson LL,Silver RM,Pandey JP.Ethnic differences in cytotoxic T lymphocyte associated antigen 4 genotype association with systemic sclerosis [J].J Rheumatol,2004,31 (1):85-7.
[10] Tan EM,Cohen AS,Fries JF,et al.The 1982 revised criteria for the classification of systemic lupus erythematosus [J].Arthritis Rheum,1982,25(11):1271-7.
[11] Aguilar F,Torres B,Sanchez-Roman J,et al.CTLA4 polymorphism in Spanish patients with systemic lupus erythematosus [J].Hum Immunol,2003,64(10):936-40.
[12] Dariavach P,Mattei MG,Golstein P,et al.Human Ig superfamily CTLA4 gene:chromosomal localization and identify of protein sequence between murine and human CTLA4 cytoplasmic domains[J].EurJ Immunogenet,1988,18(12):1901-5.
[13] Waterhouse P,Penninger JM,Timms E,et al.Lymphopropliferative disorders with early lethality in mice deficient in CTLA-4 [J].Science,1995,270(5238):985-8.
[14] Tivol EA,Borriello F,Schweitzer AN,et al.Loss of CTLA-4 leads to massive lymphoproliferation and fatal multiorgan tissue destruction,revealing a critical negative regulatory role ofCTLA-4 [J].Immunity,1995,3(5):541-7.
[15] Takiguchi M,Murakami M,Nakagawa I,et al.CTLA4 IgG gene delivery prevents autoantibody production and lupus nephritis in MRL/lpr mice[J].Life Sci,2000,66(11):991-1001.
[16] Wang X,Huang W,Mihara M,et al.Mechanism of action of combined short-term CTLA4 Ig and antiCD40 ligand in murine systemic lupus erythematosus[J].J Immunol,2002,168(4):2046-53.
[17] Heward J,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[J].Ann Rheum Dis,1999,58(3):193-5.
[18] Lee YH,Kim Yr,Ji JD,et al.Polymorphisms of the CTLA-4 exon 1and promoter gene in systemic lupus erythematosus [J].Lupus,2001,10(9):601-5.
[19] Femandez-Blanco L,Perez-Pampin E,Gomez-Reino JJ,et al.A CTLA-4 polymorphism associated with susceptibility to systemic lupus erythematosus[J].Arthritis Rheum,2004,50(1):328-9.