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dfyy8989 发表于 2011-5-12 13:54 
核心启动子突变？
核心启动子突变 - Core promoter mutations
Association Between the Various Mutations in Viral Core
Promoter Region to Different Stages of Hepatitis B,
Ranging of Asymptomatic Carrier State to Hepatocellular
Carcinoma
Jianhua Yin , MD, PhD 1 , 10 , Jiaxin Xie , PhD 1 , 10 , Shijian Liu , MD, PhD 1 , Hongwei Zhang , MD, PhD 1 , Lei Han , MS 1 , Wenying Lu , MS 1 ,
Qiuxia Shen , MS 1 , Guozhang Xu , MS 2 , Hongjun Dong , MS 2 , Jie Shen , MD 3 , Jun Zhang , MS 3 , Jiankang Han , MD 4 , Lin Wang , MD 5 ,
Yan Liu , MS 1 , Fan Wang , MS 1 , Jun Zhao , MD 6 , Qian Zhang , MD 7 , Wu Ni , MD 8 , Hongyang Wang , MD, PhD 9 and
Guangwen Cao , MD, PhD 1
OBJECTIVES: The objective of this study was to determine the association of 19 mutations with frequencies ≥ 10 %
in the core promoter region of hepatitis B virus (HBV) with chronic hepatitis B (CHB), liver cirrhosis,
and hepatocellular carcinoma (HCC).
METHODS: Eight hundred forty-six asymptomatic hepatitis B surface antigen carriers (ASCs), 235 CHB patients,
188 cirrhosis patients, and 190 HCC patients with intact data of HBV genotyping, DNA sequencing,
and serological parameters were studied. Nucleotides with the highest frequencies in HBV genotypes
B and C from all ASCs were treated as wild-type nucleotides.
RESULTS: Mutations at nt.1674, nt.1719, nt.1762, nt.1764, nt.1846, nt.1896, and nt.1913 in genotype
C were signifi cantly associated with CHB, cirrhosis, and HCC, as compared with ASCs. C1673T,
A1726C, A1727T, C1730G, C1766T, T1768A, C1773T, and C1799G in genotype C were signifi -
cantly associated with cirrhosis compared with the CHB patients, whereas these mutations were
inversely associated with HCC compared with the cirrhosis patients. Multivariate regression analyses
showed that age, male, abnormal alanine aminotransferase (ALT), T1768A, A1762T / G1764A, and
A1846T were independently associated with cirrhosis compared with ASCs and the patients with
CHB. Age, abnormal ALT, HBV DNA ( ≥ 10 4 copies / ml), genotype C, C1653T, T1674C / G, T1753V, and
A1762T / G1764A were independently associated with HCC compared with those without HCC. Haplotypic
carriages with two or more HBV mutations were signifi cantly associated with HCC. T1674C / G,
C1653T, and T1753V were specifi c for HCC. A1762T / G1764A had a moderate sensitivity and
specifi city for HCC.
CONCLUSIONS: C1673T, A1726C, A1727T, C1730G, C1766T, T1768A, C1773T, and C1799G in genotype C are
specifi c for cirrhosis. A1846T and T1674C / G are novel factors independently associated with cirrhosis
and HCC, respectively.
SUPPLEMENTARY MATERIAL is linked to the online version of the paper at http://www.nature.com/ajg
Am J Gastroenterol 2011; 106:81–92; doi: 10.1038/ajg.2010.399; published online 19 October 2010
1 Department of Epidemiology, Second Military Medical University , Shanghai , China ; 2 Department of Infectious Disease, Municipal Center for Disease Control and
Prevention of Ningbo , Ningbo , China ; 3 Department of Infectious Disease, Municipal Center for Disease Control and Prevention of Soochow , Soochow , China ;
4 Department of Infectious Disease, Municipal Center for Disease Control and Prevention of Huzhou , Huzhou , China ; 5 Department of Infectious Disease, District
Center for Disease Control and Prevention of Yangpu , Shanghai , China ; 6 Department of Hepatobiliary Surgery, The Third Affi liated Hospital, Second Military
Medical University , Shanghai , China ; 7 Department of Infectious Disease, The First Affi liated Hospital, Second Military Medical University , Shanghai , China ;
8 Department of Infectious Disease, The Second Affi liated Hospital, Second Military Medical University , Shanghai , China ; 9 Laboratory for Signal Transduction, The
Third Affi liated Hospital, Second Military Medical University , Shanghai , China ; 10 These authors contributed equally to this work . Correspondence: Guangwen Cao,
MD, PhD , Department of Epidemiology, Second Military Medical University , 800 Xiangyin Road, Shanghai 200433, China . E-mail: [email protected]
Received 7 December 2009; accepted 15 September 2010
协会之间的各种突变病毒核心
启动子区的B型肝炎的不同阶段，
测距无症状携带者肝国
癌
建华贤博士1，10，嘉兴谢，博士1，10，刘诗笺，博士1，宏伟章博士1，雷汉，硕士一，蚊蝇路，硕士1
Qiuxia沉，硕士1，许国章，硕士2，鸿钧东，硕士2，沉杰，医师3，张军，硕士3，建康韩医师4，林旺医师5
闫流，硕士一，范王，硕士一，赵军，医师6，钱张医师7，吴倪医师8日，红阳王，博士9
曹广文博士1
目标：本研究的目的是要确定对19例突变频率协会≥10％
在乙型肝炎病毒（HBV）的核心启动子慢性乙型肝炎（CHB），肝硬化地区，
与肝细胞肝癌（HCC）。
方法：8百四六无症状乙肝表面抗原携带者（先进的结构陶瓷），235例慢性乙型肝炎患者，
肝硬化188例，190肝癌与乙肝病毒基因分型，DNA测序完整资料的病人，
和血清学参数进行了研究。在乙肝病毒基因型的核苷酸频率最高
B和C所有先进的结构陶瓷被视为野生型核苷酸。
结果：突变在nt.1674，nt.1719，nt.1762，nt.1764，nt.1846，nt.1896，并在基因型nt.1913
C组cantly慢性乙肝，肝硬化和肝癌相关显，与先进的结构陶瓷比较。 C1673T，
A1726C，A1727T，C1730G，C1766T，T1768A，C1773T和C1799G基因型C组显 -
cantly与乙肝相关肝硬化患者相比，而这些突变
负相关与肝癌相比，肝硬化患者。多元回归分析
结果显示，年龄，男性，异常谷丙转氨酶（ALT），T1768A，区A1762T / G1764A，和
A1846T的独立相关较先进的结构陶瓷和肝硬化患者的
慢性乙型肝炎。年龄，ALT异常，乙肝病毒脱氧核糖核酸（≥10 4拷贝/毫升），C型，C1653T，T1674C /克，T1753V，和
区A1762T / G1764A与肝癌相关的独立与无肝癌者。单倍型
有两个或更多乙肝病毒突变马车cantly与肝癌相关的显。 T1674C /克，
C1653T和T1753V被specifi C的肝癌。区A1762T / G1764A有中度敏感性和
specifi市肝癌。
结论：C1673T，A1726C，A1727T，C1730G，C1766T，T1768A，C1773T和C1799G基因型C的
specifi C的肝硬化。 A1846T和T1674C / G是独立与肝硬化的小说因素
和肝癌，分别为。
补充材料是与纸张的在线版本在http://www.nature.com/ajg
上午胃肠病学杂志2011; 106:81-92;分类号：10.1038/ajg.2010.399;网上公布2010年10月19日
1流行病学系，第二军医大学，上海，中国; 2传染病部，市疾病预防控制中心和
预防宁波，宁波，中国3传染病，疾病控制和东吴，东吴，中国预防市委中心处;
4部传染病，疾病控制和湖州，湖州，中国预防市委中心5处传染病，区
美国疾病控制和预防杨浦，上海，中国中心6肝胆外科，第三阿菲部liated医院，第二军医
医科大学，上海，中国; 7传染病，首先阿菲部liated医院，第二军医大学，上海，中国;
8部传染病，二阿菲liated医院，第二军医大学，上海，中国，9信号转导，化验所
第三阿菲liated医院，第二军医大学，上海，中国; 10这些作家同样对这项工作作出贡献。通讯：广文曹
博士，上海200433流行病学，第二军医大学，800翔殷路，中国。电子邮箱：[email protected]
收到2009年12月7日，接受2010年9月15日
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发表于 2011-5-8 22:55
