title: Hepatitis B virus subgenotype C2- and B2-associated mutation patterns may be responsible for liver cirrhosis and hepatocellular carcinoma, respectively.
abstract: The objective of this study was to examine hepatitis B virus (HBV) subgenotypes and mutations in enhancer II, basal core promoter, and precore regions of HBV in relation to risks of liver cirrhosis (LC) and hepatocellular carcinoma (HCC) in Southeast China. A case-control study was performed, including chronic hepatitis B (CHB; n=125), LC (n=120), and HCC (n=136). HBV was genotyped by multiplex polymerase chain reaction and subgenotyped by restriction fragment length polymorphism. HBV mutations were measured by DNA sequencing. HBV genotype C (68.2%) predominated and genotype B (30.2%) was the second most common. Of these, C2 (67.5%) was the most prevalent subgenotype, and B2 (30.2%) ranked second. Thirteen mutations with a frequency >5% were detected. Seven mutation patterns (C1653T, G1719T, G1730C, T1753C, A1762T, G1764A, and G1799C) were associated with C2, and four patterns (C1810T, A1846T, G1862T, and G1896A) were associated with B2. Six patterns (C1653T, G1730C, T1753C, A1762T, G1764A, and G1799C) were obviously associated with LC, and 10 patterns (C1653T, G1730C, T1753C, A1762T, G1764A, G1799C, C1810T, A1846T, G1862T, and G1896A) were significantly associated with HCC compared with CHB. Four patterns (C1810T, A1846T, G1862T, and G1896A) were significantly associated with HCC compared with LC. Multivariate regression analyses showed that HBV subgenotype C2 and C2-associated mutation patterns (C1653T, T1753C, A1762T, and G1764A) were independent risk factors for LC when CHB was the control, and that B2-associated mutation patterns (C1810T, A1846T, G1862T, and G1896A) were independent risk factors for HCC when LC was the control.
authors.affiliation: Affiliated Hangzhou Hospital, Nanjing Medical University, Department of Laboratory Medicine, Hangzhou, China.
authors.forename: Y M
authors.initials: YM
authors.lastname: Chen
authors.forename: S H
authors.initials: SH
authors.lastname: Wu
authors.forename: C N
authors.initials: CN
authors.lastname: Qiu
authors.forename: D J
authors.initials: DJ
authors.lastname: Yu
authors.forename: X J
authors.initials: XJ
authors.lastname: Wang
mesh_terms: D000328:Adult; D000368:Aged; D000410:Alanine Transaminase / Q000097:blood; D001663:Bilirubin / Q000097:blood; D006528:Carcinoma, Hepatocellular / Q000821:virology*; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D002681:China; D005260:Female; D005838:Genotype; D006512:Hepatitis B Core Antigens / Q000235:genetics; D006515:Hepatitis B virus / Q000145:classification / Q000235:genetics*; D006801:Humans; D008103:Liver Cirrhosis / Q000821:virology*; D008113:Liver Neoplasms / Q000821:virology*; D008297:Male; D008875:Middle Aged; D060885:Multiplex Polymerase Chain Reaction; D009154:Mutation / Q000235:genetics*; D012150:Polymorphism, Restriction Fragment Length; D012307:Risk Factors; D012709:Serum Albumin / Q000032:analysis
chemical_list: D006512:Hepatitis B Core Antigens; D012709:Serum Albumin; D000410:Alanine Transaminase; D001663:Bilirubin
references.citation: J Virol. 1990 Jun;64(6):2802-9
references.pmid: 1692348
references.citation: Rev Med Virol. 1999 Jul;9(3):183-209
references.pmid: 10479779
references.citation: PLoS One. 2012;7(9):e46345
references.pmid: 23029487
references.citation: Am J Gastroenterol. 2011 Jan;106(1):81-92
references.pmid: 20959817
references.citation: J Viral Hepat. 2007 Jan;14(1):64-9
references.pmid: 17212646
references.citation: Hepatol Res. 2005 Nov;33(3):216-24
references.pmid: 16257576
references.citation: Proc Natl Acad Sci U S A. 1994 Apr 26;91(9):4077-81
references.pmid: 8171038
references.citation: Gastroenterology. 2000 Mar;118(3):554-9
references.pmid: 10702206
references.citation: PLoS One. 2012;7(6):e38394
references.pmid: 22675557
references.citation: J Natl Cancer Inst. 2009 Aug 5;101(15):1066-82
references.pmid: 19574418
references.citation: Clin Liver Dis. 2001 May;5(2):361-79
references.pmid: 11385968
references.citation: J Clin Virol. 2010 Mar;47(3):243-7
references.pmid: 20080060
references.citation: Hepatol Res. 2010 Jan;40(1):14-30
references.pmid: 20156297
references.citation: Gut. 2008 Jan;57(1):98-102
references.pmid: 17483190
references.citation: Chin Med J (Engl). 2011 Dec;124(24):4178-83
references.pmid: 22340383
references.citation: Gut. 2003 Nov;52(11):1630-7
references.pmid: 14570734
references.citation: Hepatol Res. 2008 Jun;38(6):580-92
references.pmid: 18201182
references.citation: J Viral Hepat. 1998 Jul;5(4):241-8
references.pmid: 9751010
references.citation: Clin Infect Dis. 2004 May 1;38(9):1222-8
references.pmid: 15127332
references.citation: Virus Res. 2007 Aug;127(2):177-84
references.pmid: 17280734
references.citation: Gastroenterology. 2007 Nov;133(5):1452-7
references.pmid: 17920063
references.citation: J Hepatol. 1991 Nov;13(3):372-4
references.pmid: 1808228
references.citation: Pathol Res Pract. 2008;204(10):731-42
references.pmid: 18597951
references.citation: Gut. 2008 Jan;57(1):91-7
references.pmid: 17502344
references.citation: J Med Virol. 2007 Sep;79(9):1293-304
references.pmid: 17607788
references.citation: J Gastroenterol Hepatol. 2011 Jan;26 Suppl 1:123-30
references.pmid: 21199523
references.citation: Clin Gastroenterol Hepatol. 2004 Jan;2(1):64-71
references.pmid: 15017634
references.citation: J Hepatol. 2008 Nov;49(5):718-25
references.pmid: 18801591
references.citation: J Clin Microbiol. 2007 May;45(5):1491-6
references.pmid: 17376881
references.citation: J Natl Cancer Inst. 2008 Aug 20;100(16):1134-43
references.pmid: 18695135
references.citation: J Clin Microbiol. 2002 Apr;40(4):1207-9
references.pmid: 11923332
references.citation: Hepatology. 2004 Oct;40(4):790-2
references.pmid: 15382157
references.citation: J Hepatol. 2007 Sep;47(3):366-72
references.pmid: 17561304
references.citation: Proc Natl Acad Sci U S A. 1996 May 28;93(11):5647-52
references.pmid: 8643631
references.citation: PLoS One. 2012;7(8):e42891
references.pmid: 22905181
references.citation: Liver Int. 2007 Sep;27(7):983-8
references.pmid: 17696938
references.citation: Gastroenterology. 2003 Feb;124(2):327-34
references.pmid: 12557138
references.citation: World J Gastroenterol. 2007 Jan 7;13(1):14-21
references.pmid: 17206751