IFN-γ基因多态性与HBV感染及原发性肝细胞癌易感性的研究  

Study on Susceptibility of HBV Infection and Primary Hepatocellular Carcinoma with Gene Polymorphism of IFN-gamma

作　　者：柏桦[1] 仇小强[1,2] 刘顺[1] 贝春华[3] 曾小云[1] 余红平[1] 

机构地区：[1]广西医科大学公共卫生学院流行病学教研室,南宁530021 [2]桂林医学院公共卫生学院 [3]桂林医学院科技处

出　　处：《肿瘤防治研究》2012年第3期329-334,共6页Cancer Research on Prevention and Treatment

基　　金：国家自然科学基金资助项目(30860247);广西自然科学基金资助项目(0832017Z);广西科学研究与技术开发资助项目(桂科攻0993003D-4)

摘　　要：目的探讨细胞因子IFN-γ基因-1615C/T和+5171A/G位点单核苷酸多态性在广西人群中的分布及其对原发性肝细胞癌(HCC)发生、乙型肝炎病毒(HBV)感染的影响。方法设计以医院为基础的病例对照研究,对375名HCC患者、377名HBV携带者和406健康对照进行频数匹配,采用Taq-Man MGB实时荧光定量PCR技术对上述位点进行分型。应用Logistic回归模型分析基因型在三组中的分布差异及基因环境交互作用,并进行连锁不平衡和单倍型分析。结果 -1615C/T和+5171 A/G位点的基因多态性在三组中分布差异无统计学意义(P>0.05)。Logistic回归分析结果显示,吸烟、饮酒和肝癌相关家族史与基因存在交互作用;饮酒联合-1615C/T位点突变型基因T能增加HBV感染风险(OR=1.72,95%CI:1.11～3.26);两个位点的突变型基因T和G联合肝癌相关家族史能增加HCC患病风险(OR:29.24、52.03,95%CI:6.91～123.6、7.02～385.4)。IFN-γ的-1615C/T和+5171A/G位点存在连锁不平衡(D′=0.976,P=2.22-16),但单倍型分布在HCC组与总对照组(HBV携带者对照和健康对照)间无统计学差异。结论IFN-γ的-1615C/T和+5171A/G位点的突变型基因可能不是广西人患HCC和感染HBV的直接危险因素,但环境危险因素对HCC发生和HBV感染有协同作用。Objective To explore the distribution of cytokines IFN-gamma gene（-1615C/T and ＋5171A/G）single nucleotide polymorphisms in Guangxi people,and the impact of hepatitis B virus（HBV）infection and primary hepatocellular carcinoma（HCC）occurrence.Methods A case-control study based on hospital was carried out and all the objects were frequency matched by 375 HCC patients-377 HBV carriers-406 healthy control.TaqMan MGB Real-Time fluorescence quantitative PCR technology was applied to detect the SNPs of the two loci.The distribution of the genotype and the interaction of gene-environment in the three groups were analyzed by Logistic regression model.The linkage disequilibrium and haplotype of IFN-gamma gene were analyzed.Results There was no significant statistically difference in the polymorphisms of-1615C/T and ＋5171A/G loci among the three groups（P0.05）.There were gene-environment interactions in smoking,alcohol consumption,liver cancer related family history with IFN-gamma gene according to logistic regression analysis.Alcohol consumption combined-1615 locus mutant gene G increased HBV infection risk（OR=1.72,95%CI：1.11~3.26）.The two loci mutant genes combined with liver cancer related family history also enhanced HCC risk（OR：29.24,52.03,95%CI：6.91~123.6,7.02~385.4,respectively）.-1615C/T and ＋5171A/G sites on IFN-gamma had linkage disequilibrium（D′=0.976,P=2.22-16）,but the haplotypes between HCC groups and the total controls（HBV carriers and healthy control）had no significant statistically difference.Conclusion The mutant genes of-1615C/T and ＋5171A/G loci might not influence the occurrence of HCC and HBV infection directly in the population of Guangxi,however they enhanced the risk interacted with the environment risk factors.

关 键 词：原发性肝细胞癌 HBV感染 IFN-Γ 基因多态性 

分 类 号：R181.2[医药卫生—流行病学] R735.7[医药卫生—公共卫生与预防医学]