CTLA-4基因多态性与肝细胞癌易感性的相关分析  

Analysis on correlation between cytotoxic T lymphocyte antigen 4 gene polymorphisms and susceptibility to hepatocellular carcinoma

作　　者：王甲甲[1] 张娟[1] 王智斌[1] 黄文芳[1] 

机构地区：[1]四川省医学科学院/四川省人民医院检验科,成都610072

出　　处：《重庆医学》2016年第9期1186-1189,共4页Chongqing medicine

基　　金：四川省卫生和计划生育委员会基金资助项目(140071)

摘　　要：目的分析细胞毒T淋巴细胞抗原4(CTLA-4)基因多态性-318T/C、CT60G/A与肝细胞癌(HCC)易感性之间的相关性。方法选取于2012年9月至2014年8月就诊于四川省人民医院的277例HCC患者及306例健康体检者作为研究对象,所有研究对象均为汉族人。抽取各研究对象外周血5mL,离心分离血清,采用化学发光法检测血清中甲胎蛋白(AFP)的水平;采用酶联免疫吸附试验(ELISA)法检测血清中白细胞介素(IL)-2、IL-4、转化生长因子-β(TGF-β)的水平。抽提全血基因组DNA,PCR扩增后直接测序法检测CTLA-4-318T/C、CT60G/A基因多态性的分布。结果 CTLA-4-318T/C,CT60G/A的3种基因型均符合Hardy-Weinberg平衡(P>0.05)。CTLA-4-318CC和CT60AA与降低HCC的风险有关,CTLA-4CT60G/A不同基因型与血清AFP水平有明显相关性(χ2=12.779,P=0.012)。携带CTLA-4-318T、CT60G等位基因的HCC患者血清中IL-2、IL-4水平明显降低,TGF-β水平显著升高,且CTLA-4-318T与HCC的分级有明显的相关性。结论 CTLA-4-318TT能够促进HCC的发生、发展,这可能与下调Th1/Th2型细胞因子,上调Th3型细胞因子有关。Objective To analyse the correlation between cytotoxic T-lymphocyte antigen-4（CTLA-4）gene polymorphism-318T/C,CT60 G/A and the susceptibility of hepatocellular carcinoma（HCC）.Methods Totally 277 cases of HCC and 306 healthy controls in our hospital from September 2012 to September 2014 were selected as the research subjects,all subjects were Han nationality.The peripheral blood（5 mL）in each case was collected for separating serum,the AFP level was detected by chemilunescent method,the serum IL-2,IL-4and TGF-βlevels were detected by ELISA.Genomic DNA was extracted,after PCR amplification,the CTLA-4-318T/C,CT60G/A gene polymorphism distributions were detected by the direct sequencing method.Results The CTLA-4-318 CC and CT60 AA genotypes all conformed to the Hardy-Weinberg equilibrium（P〉0.05）.CTLA-4-318 CC and CT60 AA were related with the HCC risk decrease,different genotypes of CTLA-4CT60G/A had obvious relation with serum AFP level（χ2=12.779,P=0.012）.The serum IL-2and IL-4levels in the HCC patients carrying CTLA-4-318 Tand CT60Gallele were significantly decreased,while the TGF-βlevel was significantly increased,moreover CTLA-4-318 had obvious relation with the HCC grading.Conclusion CTLA-4-318 TT could promote the occurrence and progression of HCC,which might be related with the down-regulation of Th1/Th2 type cytokines,and up-regulation of Th3 type cytokine.

关 键 词：细胞毒T淋巴细胞抗原4 基因多态性 肝细胞癌 细胞因子 

分 类 号：R735.7[医药卫生—肿瘤]