摘要目的 探索细胞毒性T淋巴细胞相关分子4(cytotoxic T-lymphocyte-associated protein 4,CTLA4)基因单核苷酸多态性(single nucleotide polymorphism,SNPs)与宫颈癌易感性的关系.方法 应用sequenom MassARRAY时间飞行质谱系统对100例宫颈癌及100名健康对照者 CTLA4基因20个多态位点(CTLA4_1～CTLA4_20)进行基因型分型,统计分析基因型频率和肿瘤易感性的关系.结果 与正常人群中最常见的 CTLA4基因单倍型-1576A、-318C和1402G相比,带有单倍型-1576G、-318T或1402A的个体均显著增加宫颈癌的风险(P<0.05),相对风险度的比值比及其95%可信区间分别为2.87(1.75～4.76),4.02(1.72～9.09)和4.51(1.46～13.88),而其余基因型与宫颈癌发病风险没有显著的相关性;其中rs5742909易感位点与先前的报道相一致.而双荧光素酶报告基因实验进一步证明,位于基因启动子区域的rs11571316多态位点能显著影响报告基因的表达活性.结论 CTLA4基因启动子区域的SNP可能通过影响 CTLA4基因的表达水平来影响个体对宫颈癌的易感性.

abstractsObjective To evaluate the association between single nucleotide polymorphisms (SNPs) of cytotoxic T-lymphocyte-associated protein 4 (CTLA4) gene and susceptibility to cervical cancer. Methods One hundred patients and 100 healthy controls from Hubei province were genotyped for 20 polymorphic loci using Sequenom. Results The frequency of rs11571316 G allele and rs5742909 T allele, which are localized in the promoter region, and rs11571319 A allele, which is downstream of the gene, were significantly higher in patients than in controls. Luciferase assay showed that, as the previously reported rs5742909 T allele, rs11571316 G allele could significantly increase the expression of the reporter gene. Conclusion SNPs in the promoter region of CTLA4 gene might increase the susceptibility to cervical cancer by increasing CTLA4 gene expression.