APOBEC3B基因拷贝数变异与HBV感染后不同转归的关系
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摘要
目的阐明APOBEC3B基因拷贝数在HBV感染后不同转归患者中的分布频率差异及其在临床转归中的作用。方法收集2016年1月-2017年12月于安徽医科大学第一附属医院就诊的296例HBV感染后急性自限性恢复患者和819例不同疾病阶段的慢性HBV感染者外周血标本,慢性HBV感染组中包含慢性乙型肝炎(CHB)患者444例、肝硬化(LC)患者252例和肝细胞癌(HCC)患者123例。采用AccuCopy方法检测两组患者外周血APOBEC3B基因拷贝数,同时收集上述患者的相关临床资料。各组间APOBEC3B拷贝数分布频率比较采用χ2检验。结果在HBV感染后急慢性转归方面,急性自限性恢复组APOBEC3B拷贝数减少和缺失的比例显著低于慢性HBV感染组(46. 96%vs 58. 00%,P=0. 001 1)。在慢性HBV感染后疾病进展方面,随疾病进展,APOBEC3B基因拷贝数缺失的比例在CHB、LC和HCC患者3组间逐渐增加(分别为11. 04%、14. 29%和22. 76%),差异具有统计学意义(χ2=11. 85,P=0. 019)。在慢性HBV感染组中,APOBEC3B拷贝数分布频率在HBeAg阳性组和HBeAg阴性组间差异无统计学意义(χ2=0. 639,P=0. 727)。结论 APOBEC3B基因拷贝数变异与HBV感染后的不同转归密切相关,APOBEC3B基因拷贝数减少和缺失可能是HBV感染慢性化和疾病进展的遗传易感因素。
Objective To investigate the difference in the distribution frequency of APOBEC3 B copy number variations( CNVs) betweenpatients with different outcomes after hepatitis B virus( HBV) infection and the role of APOBEC3 B CNVs in clinical outcome. MethodsA total of 296 patients with acute self-limiting recovery after HBV infection and 819 patients with different stages of chronic HBV infectionwho visited The First Affiliated Hospital of Anhui Medical University from January 2016 to December 2017 were enrolled as acute self limitingrecovery group and chronic HBV infection group,respectively,and their peripheral blood samples were collected. Among the 819 patientswith chronic HBV injection,444 had chronic hepatitis B( CHB),252 had liver cirrhosis( LC),and 123 had hepatocellular carcinoma( HCC). The AccuCopy method was used to measure APOBEC3 B CNVs in peripheral blood,and related clinical data were collected for allpatients. The chi-square test was used for comparison of distribution frequency of APOBEC3 B CNVs between groups. Results For acuteor chronic outcome after chronic HBV infection,the acute self limiting recovery group had a significantly lower proportion of patients with re-duced or deleted APOBEC3 B CNVs than the chronic HBV infection group( 46. 96% vs 58. 00%,P = 0. 001 1). For disease progression af-ter chronic HBV infection,the HCC group had the highest proportion of patients with deleted APOBEC3 B CNVs of 22. 76%,followed by theLC group( 14. 29%) and the CHB group( 11. 04%),and there was a significant difference between the three groups( χ2= 11. 85,P =0. 019). In the chronic HBV infection group,there was no significant difference in the distribution frequency of APOBEC3 B CNVs betweenthe patients with positive E-antigen and those with negative E-antigen( χ2= 0. 639,P = 0. 727). Conclusion APOBEC3 B CNV is asso-ciated with the outcome of chronic HBV infection,and reduced and deleted APOBEC3 B CNV is a genetic susceptibility factor for chronicityand progression of HBV infection.
Objective To investigate the difference in the distribution frequency of APOBEC3 B copy number variations( CNVs) betweenpatients with different outcomes after hepatitis B virus( HBV) infection and the role of APOBEC3 B CNVs in clinical outcome. MethodsA total of 296 patients with acute self-limiting recovery after HBV infection and 819 patients with different stages of chronic HBV infectionwho visited The First Affiliated Hospital of Anhui Medical University from January 2016 to December 2017 were enrolled as acute self limitingrecovery group and chronic HBV infection group,respectively,and their peripheral blood samples were collected. Among the 819 patientswith chronic HBV injection,444 had chronic hepatitis B( CHB),252 had liver cirrhosis( LC),and 123 had hepatocellular carcinoma( HCC). The AccuCopy method was used to measure APOBEC3 B CNVs in peripheral blood,and related clinical data were collected for allpatients. The chi-square test was used for comparison of distribution frequency of APOBEC3 B CNVs between groups. Results For acuteor chronic outcome after chronic HBV infection,the acute self limiting recovery group had a significantly lower proportion of patients with re-duced or deleted APOBEC3 B CNVs than the chronic HBV infection group( 46. 96% vs 58. 00%,P = 0. 001 1). For disease progression af-ter chronic HBV infection,the HCC group had the highest proportion of patients with deleted APOBEC3 B CNVs of 22. 76%,followed by theLC group( 14. 29%) and the CHB group( 11. 04%),and there was a significant difference between the three groups( χ2= 11. 85,P =0. 019). In the chronic HBV infection group,there was no significant difference in the distribution frequency of APOBEC3 B CNVs betweenthe patients with positive E-antigen and those with negative E-antigen( χ2= 0. 639,P = 0. 727). Conclusion APOBEC3 B CNV is asso-ciated with the outcome of chronic HBV infection,and reduced and deleted APOBEC3 B CNV is a genetic susceptibility factor for chronicityand progression of HBV infection.
引文
[1] BUSCH K,THIMME R. Natural history of chronic hepatitis B virusinfection[J]. Med Microbiol Immunol,2015,204(1):5-10.
[2] KRAWCZYK M,MULLENBACH R,WEBER SN,et al. Genome-wide association studies and genetic risk assessment of liver dis-eases[J]. Nat Rev Gastroenterol Hepatol,2010,7(12):669-681.
[3] JAKOBSSON M,SCHOLZ SW,SCHEET P,et al. Genotype,haplotype and copy-number variation in worldwide humanpopulations[J]. Nature,2008,451(7181):998-1003.
[4] HOLLOX EJ,HOH BP. Human gene copy number variationand infectious disease[J]. Hum Genet,2014,133(10):1217-1233.
[5] BUDZKO L,MARCINKOWSKA-SWOJAK M,JACKOWIAK P,et al. Copy number variation of genes involved in the hepatitisC virus-human interactome[J]. Sci Rep,2016,6:31340.
[6] LIU SJ,YAO L,DING D,et al. CCL3L1 copy number varia-tion and susceptibility to HIV-1 infection:A meta-analysis[J]. PLo S One,2010,5(12):e15778.
[7] BONVIN M,GREEVE J. Hepatitis B:Modern concepts inpathogenesis-APOBEC3 cytidine deaminases as effectors ininnate immunity against the hepatitis B virus[J]. Curr Opin In-fect Dis,2008,21(3):298-303.
[8] KITAMURA S,ODE H,NAKASHIMA M,et al. The APO-BEC3C crystal structure and the interface for HIV-1 Vif bind-ing[J]. Nat Struct Mol Biol,2012,19(10):1005-1010.
[9] CHEN YM,HU J,CAI XF,et al. APOBEC3B edits HBV DNAand inhibits HBV replication during reverse transcription[J].Antiviral Res,2018,149:16-25.
[10] PRASETYO AA,SARYATUN R,REVIONO,et al. The APO-BEC3B deletion polymorphism is associated with prevalence ofhepatitis B virus,hepatitis C virus,Torque Teno virus,andToxoplasma gondii co-infection among HIV-infected individ-uals[J]. J Clin Virol,2015,70:67-71.
[11] DU RQ,LU CC,JIANG ZW,et al. Efficient typing of copynumber variations in a segmental duplication-mediated rear-rangement hotspot using multiplex competitive amplification[J]. Hum Genet,2012,57(8):545-551.
[12] EZZIKOURI S,KITAB B,REBBANI K,et al. Polymorphic APO-BEC3 modulates chronic hepatitis B in Moroccan population[J].J Viral Hepat,2013,20(10):678-686.
[13] SINGH H,MARATHE SD,NAIN S,et al. APOBEC3B deletionimpacts on susceptibility to acquire HIV-1 and its advance-ment among individuals in western India[J]. APMIS,2016,124(10):881-887.
[14] IMAHASHI M,IZUMI T,WATANABE D,et al. Lack of associationbetween intact/deletion polymorphisms of the APOBEC3B geneand HIV-1 risk[J]. PLo S One,2014,9(3):e92861.
[15] ZHANG TW,CAI JQ,CHANG J,et al. Evidence of associa-tions of APOBEC3B gene deletion with susceptibility to persis-tent HBV infection and hepatocellular carcinoma[J]. Hum MolGenet,2013,22(6):1262-1269.
[16] KIDD JM,NEWMAN TL,TUZUN E,et al. Population stratifica-tion of a common APOBEC gene deletion polymorphism[J].PLo S Genet,2007,3(4):e63.
[2] KRAWCZYK M,MULLENBACH R,WEBER SN,et al. Genome-wide association studies and genetic risk assessment of liver dis-eases[J]. Nat Rev Gastroenterol Hepatol,2010,7(12):669-681.
[3] JAKOBSSON M,SCHOLZ SW,SCHEET P,et al. Genotype,haplotype and copy-number variation in worldwide humanpopulations[J]. Nature,2008,451(7181):998-1003.
[4] HOLLOX EJ,HOH BP. Human gene copy number variationand infectious disease[J]. Hum Genet,2014,133(10):1217-1233.
[5] BUDZKO L,MARCINKOWSKA-SWOJAK M,JACKOWIAK P,et al. Copy number variation of genes involved in the hepatitisC virus-human interactome[J]. Sci Rep,2016,6:31340.
[6] LIU SJ,YAO L,DING D,et al. CCL3L1 copy number varia-tion and susceptibility to HIV-1 infection:A meta-analysis[J]. PLo S One,2010,5(12):e15778.
[7] BONVIN M,GREEVE J. Hepatitis B:Modern concepts inpathogenesis-APOBEC3 cytidine deaminases as effectors ininnate immunity against the hepatitis B virus[J]. Curr Opin In-fect Dis,2008,21(3):298-303.
[8] KITAMURA S,ODE H,NAKASHIMA M,et al. The APO-BEC3C crystal structure and the interface for HIV-1 Vif bind-ing[J]. Nat Struct Mol Biol,2012,19(10):1005-1010.
[9] CHEN YM,HU J,CAI XF,et al. APOBEC3B edits HBV DNAand inhibits HBV replication during reverse transcription[J].Antiviral Res,2018,149:16-25.
[10] PRASETYO AA,SARYATUN R,REVIONO,et al. The APO-BEC3B deletion polymorphism is associated with prevalence ofhepatitis B virus,hepatitis C virus,Torque Teno virus,andToxoplasma gondii co-infection among HIV-infected individ-uals[J]. J Clin Virol,2015,70:67-71.
[11] DU RQ,LU CC,JIANG ZW,et al. Efficient typing of copynumber variations in a segmental duplication-mediated rear-rangement hotspot using multiplex competitive amplification[J]. Hum Genet,2012,57(8):545-551.
[12] EZZIKOURI S,KITAB B,REBBANI K,et al. Polymorphic APO-BEC3 modulates chronic hepatitis B in Moroccan population[J].J Viral Hepat,2013,20(10):678-686.
[13] SINGH H,MARATHE SD,NAIN S,et al. APOBEC3B deletionimpacts on susceptibility to acquire HIV-1 and its advance-ment among individuals in western India[J]. APMIS,2016,124(10):881-887.
[14] IMAHASHI M,IZUMI T,WATANABE D,et al. Lack of associationbetween intact/deletion polymorphisms of the APOBEC3B geneand HIV-1 risk[J]. PLo S One,2014,9(3):e92861.
[15] ZHANG TW,CAI JQ,CHANG J,et al. Evidence of associa-tions of APOBEC3B gene deletion with susceptibility to persis-tent HBV infection and hepatocellular carcinoma[J]. Hum MolGenet,2013,22(6):1262-1269.
[16] KIDD JM,NEWMAN TL,TUZUN E,et al. Population stratifica-tion of a common APOBEC gene deletion polymorphism[J].PLo S Genet,2007,3(4):e63.
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