细胞毒性T淋巴细胞相关抗原-4基因启动子区多态性与系统性红斑狼疮的遗传易感性

Cytotoxic T lymphocyte-associated antigen-4 gene promoter polymorphisms in patients with systemic lupus erythematosus in southern Chinese population

目的探讨细胞毒性T淋巴细胞相关抗原-4(cytotoxic T lymphocyte-associated antigen 4,CTLA-4)基因启动子区多态性与系统性红斑狼疮(systemic lupus erythematosus,SLE)发病的相关性。方法以医院为基础的病例对照研究,应用PCR-RFLP技术分析了97例SLE患者和200例对照在启动子区-1722T〉C和-318C〉T位点的多态性。结果SLE患者组-1722T〉C位点TT基因型频率高于对照组(P=0.002),患者中的T等位基因比例高于对照组(OR=1.94,95%CI1.34-2.80,P=0.000);而在-318C〉T位点,病例组和对照组的基因型频率和等位基因频率分布无显著差异。但是,两位点等位基因间存在连锁不平衡(精确P<0.05),且在病例组和对照组,单倍型频率分布不同(χ2=12.64,P=0.005);其中,与对照组相比,病例组中T-C单倍型具有较高的频率(P=0.001)而C-C单倍型频率较低(P=0.002)。结论CTLA-4基因-1722T〉C位点多态与SLE易感性有关。虽然本次研究结果未发现-318C〉T位点多态与SLE发病相关,但发现T-C单倍型为SLE易感单倍型,而C-C单倍型为其保护单倍型。

Purpose To assess the association between polymorphisms within Cytotoxic T lymphocyte-associated antigen-4 （CTLA-4） gene promoter and the morbidity of systemic lupus erythematosus （SLE） in Chinese people. Methods A case-control led study was performed for CTLA-4 polymorphisms, -1722 T〉C and -318 C〉T in the promoter region in 97 patients with SLE and 200 healthy individuals. We examined the CTLA-4 genotype of these subjects by polymerase chain reaction-restriction fragment length polymorphism （PCR-RFLP）. Results There was a significant difference in -1722 T〉C genotype frequencies between the two groups （P = 0. 002）. Carrier frequencies of the -1722 T allele in the promoter were significantly increased in SLE patients compared with those in controls （odds ratio = 1.94. 95% confidence intereal： 1. 34 - 2. 80. P= 0. 000）. There was no difference in -318 C〉T genelype and allele frequencies between the two groups. However. there was a linkage disequilibrium between the -1722 T〉C and -318 C〉T. There was a significant difference in CTLA-4 haplotype distrihution between the two groups （X^2= 12.64. P =0.005）, which the relative high pro portiere was T-C haplotype （ P = 0.001） and the less one was C-C haplotype （ P = 0. 002） in SLE group, compared to control group. Conclusions The 1722 T〉C in the promoter of CTLA 4 was determined to be susceptible to SLE in southern Chinese population, Although the resuh showed that -318 C〉T was not responsible for SLE. the T -C hapiotype might be a susceptible haplotype and C-C haplotype a protective one in southern Chinese population.