CTLA-4基因CT60标记与系统性红斑狼疮的相关性研究  

Study on the correlation between CT 60 marker of the CTLA-4 gene and systemic lupus erythematosus

作　　者：余文辉[1] 周小梅[1] 花纯宏[1] 李顺民[2] 周大桥[2] 张剑勇[3] 刘鸿禧[4] 

机构地区：[1]深圳市中医院检验科,518033 [2]深圳市中医院内科,518033 [3]深圳市中医院风湿免疫科,518033 [4]汕头大学医学院医学遗传学教研室,515031

出　　处：《国外医学（临床生物化学与检验学分册）》2005年第11期769-772,共4页Foreign Medical Sciences(section of Clinical Biochemistry and Laboratory Medicine

摘　　要：目的研究细胞毒性T淋巴细胞相关抗原-4(CTLA-4)基因CT60标记与系统性红斑狼疮(SLE)的相关性.方法利用聚合酶链反应-限制性片段长度多态性分析(PCR-RFLP)对45例SLE患者和63名健康对照者进行CT60基因分型.采用荧光定量(FQ)-PCR法进行3′-非翻译区(3′-UTR)微卫星阵列(AT)n多态性基因分型,对CTLA-4基因3′-UTR微卫星阵列(AT)n与-1722T/C、-319C/T、+49A/G基因多态性进行分析,以求证CTLA-4单倍型与SLE的关系.结果在CT60A/G分型中,SLE患者AA基因型频率明显低于对照组(20.0% vs 25.4%) ,P=0.003,校正后P (Pcorr)=0.009,优势比(odds ratio,OR)=0.58, 95% CI 0.40～0.85.即病例组G基因表型频率高于对照组(80.0% vs 74.6%), P=0.009, Pcorr=0.006, OR=1.71, 95% CI 1.18～2.49.患者组与对照组的等位基因频率分布也明显不同(P=0.01),Pcorr=0.02, OR (等位基因G)=1.32,95% CI 1.06～1.65.结合不同基因多态性资料进行分析后,发现2个中性单倍型基因:+49A;(AT)7;CT60A和+49G;(AT)8～19;CT60G.此外,也发现易感性单倍型基因+49A;(AT)>19;CT60G.结论 CTLA-4基因3′-UTR为SLE易感性基因片段.Objective To investigate the possible correlation between CT 60 marker of the cytotoxic T lymphocyte antigen-4 （CTLA-4） gene and systemic lupus erythematosus （SLE）. Methods Genotyping of the CT60 was performed in 45 patients with SLE and 63 healthy controls using polymerase chain reaction-restriction fragment length polymorphism （PCR-RFLP） analysis. Genotyping of microsatellite polymorphisms （AT）n in the 3＇-untranslated region （3＇-UTR） was performed using fluorescence quantitative-PCR,and to identify the possible CTLA-4 haplotype responsible for the association,taking into account other polymorphisms decribed at positions -1722 T/C,-319 C/T, ＋49 A/G, and the microsatellite （AT）n in the 3＇-untranslated region （UTR） of the CTLA-4 gene. Results With regard to CT60 A/G, the frequency of the AA genotype was significantly decreased among the SLE patients （20.0% vs 25.4 % in the controls group; P = 0. 003, corrected P [Pcorr] = 0. 009, odds ratio [OR]=0.58,95% confidence interval [CI]0. 40-0. 85）. In other words, the frequency of individuals bearing the G phenotype was increased in the patients group compared with the control group （80.0% vs 74.6 % ; P = 0. 003, Pcorr = 0. 006, OR= 1.71,95 % CI 1.18- 2.49）. The distribution of the allele frequency was also significantly different between patients and controls （P=0.01, Pcorr = 0.02,OR [for allele G] = 1.32,95% CI 1.06-1.65）. After combining the data on different polymorphisms, 2 neutral haplotypes were found： ＋ 49A; （AT）7 ; CT60A and ＋ 49G; （AT）8-19 ; CT60G. In addition, a susceptibility haplotype was found： ＋49A; （AT）〉19 ;CT60G. Conclusion The 3＇-UTR of the CTLA-4 gene is involved in susceptibility to SLE.

关 键 词：红斑狼疮 系统性 聚合酶链反应 

分 类 号：R593.241[医药卫生—内科学]