Journal of Capital Medical University ›› 2011, Vol. 32 ›› Issue (3): 324-330.doi: 10.3969/j.issn.1006-7795.2011.03.003

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Mutation profiles of basic core promoter and precore and pres in patients with chronic hepatitis B virus infection and their clinical implications

ZHANG Xin1#, WU Yan-ning1#, ZHANG Da-ke2, DONG Pei-ling1, FAN Chun-lei1, LI Lei1, 1*
  

  1. 1. Department of Gastroenterology and Hepatology, Beijing Youan Hospital, Capital Medical University, Beijing 100069, China; 2. Key Laboratory of Genome Sciences and information, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100029, China
  • Received:1900-01-01 Revised:1900-01-01 Online:2011-06-21 Published:2011-06-21
  • Contact: DING Hui-guo

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Abstract: ObjectiveTo analyze the mutation profiles and their implications of basic core promoter(BCP), precore(PC) and pres in patients with chronic hepatitis B virus(HBV) infection.
MethodsTotally 180 patients with chronic HBV infection were included. Of them, 13 were asyptomatic hepatitis B virus carriers(CC), 75 were chronic hepatitis(CH) patients, 62 and 30 were cases with HBV related liver cirrhosis(LC) or carcinoma(HCC). Serum HBVDNA was extracted using QIAamp DNA MiniKit and the BCP/PC and PreS genes were amplified with routine PCR. The gene sequence was directly measured using ABI377 DNA sequencing machine. If sequencing failed, cloning products were also sequenced. The bioinformatics were analyzed with SeqMan software.
ResultsMutation profiles of bcp/pc included nt 1753, nt 1762, nt 1764, nt 1776, nt 1803, nt1846 and nt 1896. The mutation frequency of nt 1762（nt 1764）in patients with CC, CH, LC and HCC were 7.7%, 68.0%, 72.7%（68.0%） and 90.9%（81.8%）, respectively. The frequency of G1896A mutation in HCC patients was 54.6%. A1762T+G1764A, A1762T+G1764A+G1896A or T1753A/C+A1762T+G1764A+
G1896A was 36%,11%,7%,respectively. The mutation frequency of A1727G in LC and HCC patients were 72% and 63%. There were more mutations in HBeAg negative patients（P=0.022）. G1776A and G1896A mutation were independently predicted HBeAg loss(P＜0.05). The deletion frequency of PreS1, PreS2 and PreS1+S2 were 41.2%, 58.8%, 29.4% in LC patients and 7.1%, 71.4%, 7.1% in HCC patients(P＜0.05).
Conclusion Mutations of A1727G, A1762T, G1764A and A1762T+G1764A and PreS deletion were more common in HBV related LC and HCC patients. G1776A and G1896A mutations were independently related to HBeAg loss. A1762T and G1764A mutations and PreS deletions may early predict HCC development, although this warrants further studies.

Key words: hepatitis B virus, bcp/pc mutation, combination mutation, pres deletion

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