HBV基因型、基因亚型及基因变异与原发性肝癌的关系

Correlation of hepatocellular carcinoma with hepatitis B virus genotype, subgenotype, and mutation

目的探讨乙型肝炎病毒(HBV)不同基因型、基因亚型及基因变异与原发性肝癌(PHC)的关系,为制定PHC的预防和治疗措施提供科学依据。方法收集新疆生产建设兵团医院2013年3月至2016年3月共4例感染HBV基础上的PHC患者,利用荧光定量PCR法检测HBV DNA,酶联免疫法检测HBeAg。应用PCR方法检测患者HBV基因型、基因亚型分布特征,检测HBV基因变异情况。结果此4例感染HBV基础上的PHC患者中,3例患者HBeAg(+),HBeAg阳性率为75%。4例患者中3例HBV DNA(+),定量检测结果分别为2.03×105 IU/ml、2.56×106 IU/ml、3.12×105 IU/ml;1例患者HBV DNA(-)。检测患者基因型为B型1例(B2亚型),C型3例(C1亚型1例,C2亚型2例)。HBV B2亚型、C1亚型和1例C2亚型患者,分别在APC、CTNNB1、IGF2R基因处出现基因变异;1例C2亚型患者(80岁),在UGT1A5、ZFYVE16、MALRD1基因的外显子序列检测中发现移码变异。结论 HBV基因型,尤其是C型可能是PHC发生的危险因素。基因变异与PHC的发生发展可能也存在密切关系。

Objective To analyze the correlation of hepatocellular carcinoma with hepatitis B virus genotype,subgenotype,or mutation,so as to provide a scientific basis for the prevention of hepatocellular carcinoma.Methods Totally four patients with HBV associated primary hepatocellular carcinoma(PHC)were collected in this study.HBV DNA was tested by qRT-PCR.HBeAg was tested by enzyme linked immunosorbent assay.HBV genotypes were determined by PCR-restriction fragment length polymorphism.HBV subgenotypes were determined by nested PCR.HBV DNA mutations were determined by PCR or direct sequencing.Results Among the four patients with PHC,the positive rate of HBeAg was 75%.HBV DNA quantitative detection was positive in three patients(2.03×10^5 IU/mL,2.56×10^6 IU/mL,and 3.12×10^5 IU/mL),and one case was HBV DNA negative.The detected genotypes included type B in one case(subtype B2)and type C in three cases,among which one was subtype C1 and two were subtype C2.Thus,in PHC patients,the main genotype and subgenotype were C and C2,respectively.Conclusion HBV genotypes,especially genotype C and subgenotype C2 variants,may be risk factors for the development of PHC.The gene mutations of HBV DNA may be closely related to the occurrence and development of PHC.