CTLA-4基因启动子区多态性与系统性红斑狼疮的关系分析

目的分析细胞毒性T淋巴细胞相关抗原-4(CTLA-4)基因启动子区-1722和-318位点多态性与系统性红斑狼疮(SLE)的关联性。方法利用聚合酶链反应-限制性片段长度多态性分析方法对112例患者和110例健康者检测-1722位点胸腺嘧啶/胞嘧啶(T/C)和-318位点T/C的多态性,并进行基因扩增,依据各条带相对分子质量的大小对CTLA-4基因-1722位点T/C和-318位点T/C进行分型。结果以组一为例,CTLA-4基因-1722位点TC基因型频率明显升高,差异有统计学意义(32%vs31%,P=0.015,OR=0.618);CC基因型频率明显升高,差异也有统计学意义(30%vs21%,P=0.039,OR=1.586);TT基因型频率虽有降低趋势,但差异无统计学意义(0%vs7%,P=0.346,OR=1.008),SLE组和健康对照组CTLA-4基因-1722位点等位基因C基因型频率明显升高,差异有统计学意义(61%vs68%,P=0.053,OR=1.781);携带者C基因型频率明显降低,差异也有统计学意义(52%vs59%,P=0.040,OR=1.652)。另外列出了CTLA-4基因-1722位点TC、CC和TT基因型的电泳结果及CTLA-4基因-318位点PCR单扩结果。结论 CTLA-4基因启动子区-1722的TC、CC基因可能是SLE易感性的一个危险因子,CTLA-4基因启动子区-1722基因型和CTLA-4基因启动子区-1722和-318位点的活性水平可作为推测SLE易感性的参考指标。

The relationship between polymorphism in promoter of CTLA-4 gene and systemic lupus erythmatosus

Objective To study the polymorphism at position -1722 and -318 in promoter of cytotoxic T lym- phocyte antigen 4（CTLA-4） gene in systemic lupus erythematosus（SLE）. Methods The genotypes at position -1722 and 318 in promoter of CTI.A 4 gene were determined by polymerase chain reaction-restriction fragment length pol- ymorphism（PCR-RFLP） method in 112 patients with SLE and 110 cases of ethnically-matched controls in China. Re- sults Taking column one for example, the frequencies of TC genotypes at position -1722 in promoter of CTLA 4 gene in patients with SEE were obviously higher（32% vs 31% ,P=0. 015,0R=0. 618）. The frequencies of CC geno types at position -1722 in promoter of CTLA-4 gene in the patients with SIrE were obviously higher（30% vs 21%, P=0. 039,OR=1. 586）. Although the frequencies of TT genotypes at position -1722 in promoter of CTLA 4 gene in the patients with SI.E were rather lower,the frequencies of genotypes（0% vs 7% ,P=0. 346,OR= 1. 008）in the pa- tients with SI.E were not significantly different from those in controls. The frequencies of C allele at position -1722 in promoter of CTLA-4 gene in patients with SLE were obviously higher（61% vs 68%, P=0. 053, OR=1. 781 ）. The frequencies of C allele at position -1722 in promoter of CTLA 4 gene in the diseases carriers were obviously lower （52 %vs 59 %, P〈0. 040,OR=1. 652）. Besides, the electrophoresis diagrams of TC, CC and TT genotypes at posi tion -1722 in promoter of CTLA 4 gene in the patients with SLE appeared to be on the end here,and the electrophoresis diagrams at position 318 in promoter of CTLA-4 gene in patients with SEE also showed to be on the end here. Conclusion CC and TT genotgpes at position -1722 in promoter of CTLA-4 gene may be the risk factor of SIrE and the level of the activity of genotypes at position 1772 and -138 in promoter of CTLA-4 gene can he seen as an inferable index of SLE.