乙肝病毒前S基因变异与乙肝肝硬化的相关性研究  

Correlation between preS gene mutation of hepatitis B virus and liver cirrhosis after hepatitis B virus infection

作　　者：谢佳新 丁一波 张丽 王缚鲲[3] 张海谱 XIE Jia-xin;DING Yi-bo;ZHANG Li;WANG Fu-kun;ZHANG Hai-pu(The Third Military Medical University,Chongqing 400038,China;The Second Miliary Medical University,Shanghai 2000433,China;Bethune Hoaspital,Shijazhuang,Hebei 050000,China)

机构地区：[1]陆军军医大学,重庆400038 [2]海军军医大学,上海200433 [3]白求恩国际和平医院,河北石家庄050000

出　　处：《实用预防医学》2020年第5期547-550,共4页Practical Preventive Medicine

基　　金：国家自然科学基金(81803294);河北省自然科学基金(H2015509001)。

摘　　要：目的探讨乙型肝炎病毒(hepatitis B virus,HBV)前S基因(preS)变异与HBV感染后肝硬化发生的相关性。方法采用病例对照研究设计,对50例慢性乙型肝炎(chronic hepatitis B,CHB)患者和67例乙肝肝硬化(liver cirrhosis,LC)患者的血清HBV PreS基因进行扩增和测序,应用MEGA7软件进行序列比对,使用SPSS 16.0统计软件对PreS基因热点变异与LC的相关性进行单因素和多因素分析。结果单因素分析结果表明,HBV基因组PreS区T3116m(χ^2=8.470,P=0.004)、A49m(χ^2=4.939,P=0.026)、T53m(χ^2=6.683,P=0.010)、A109m(χ^2=5.868,P=0.015)及PreS缺失变异(χ^2=12.154,P=0.000)与LC发生显著相关。PreS缺失变异在失代偿期LC患者中的频率(63.16%)显著高于代偿期LC患者(31.03%)(P=0.007)。多因素分析结果表明,年龄越大(OR=1.07,95%CI:1.02~1.11)、T3116m(OR=4.18,95%CI:1.39~12.61)、PreS缺失变异(OR=7.20,95%CI:2.09~24.80)是LC的独立危险因素。结论HBV PreS缺失变异与T3116m是乙型肝炎患者进展至LC的危险变异,还需要大样本人群进行验证。Objective To explore the correlation of preS gene variation of hepatitis B virus(HBV)with the occurrence of liver cirrhosis(LC)after HBV infection.Methods A case-control study,including 50 patients with chronic hepatitis B(CHB)and 67 patients with LC after HBV infection,was designed.preS gene of serum HBV from all the subjects was amplified and sequenced.MEGA7 software was used to align the sequence.The correlation of mutations in HBV preS gene hot spots with LC was determined through univariate and multivariate analyses by using SPSS16.0 software.Results Univariate analysis indicated that HBV mutations in the preS region,including T3116 m(χ^2=8.470,P=0.004),A49 m(χ^2=4.939,P=0.026),T53 m(χ^2=6.683,P=0.010),A109 m(χ^2=5.868,P=0.015),and preS deletion(χ^2=12.154,P=0.000)were significantly associated with the risks of LC.The frequency of preS deletion was significantly higher in decompensatory LC patients than in compensatory LC patients(63.16%vs.31.03%,P=0.007).Multivariate analysis showed that advanced age(OR=1.07,95%CI:1.02-1.11),T3116 m(OR=4.18,95%CI:1.39-12.61),and preS deletion(OR=7.20,95%CI:2.09-24.80)were independent risk factors for LC.Conclusions HBV preS deletion and T3116 m are the HBV mutations related to higher risk of progression from CHB to LC,which need to be validated in a larger sample size.

关 键 词：乙型肝炎病毒 肝硬化 突变 基因型 

分 类 号：R183.9[医药卫生—流行病学]