Pop-up English-Chinese

Genetic Mutations of the Hepatitis B Virus Genome S and BCP/Pre-C Regions of the Hepatitis B Virus (HBV) Genome in Chronic HBV Infection in Fujian Province of China

LI Dong 1 YANG Xiuhui 1,2 CHEN Zhifei 1 ZHANG Suhan 1 ZHENG Ningxuan 1 PAN Weiyi 1,2 ZHOU Yong 1,2 ZHENG Kuicheng 1,2

(1.Key Laboratory of Zoonosis Research of Fujian Province, Fujian Center for Disease Control & Prevention , Fuzhou, China 350001)
(2.Teaching Base of Public Health School of Fujian Medical University , Fuzhou, China 350001)
【Novelty】Based on the previous study selected the sequence of HBV gene S area, basic core promoter (BCP) and the Pre- C mutation as a key discussion,More than previous articles is one of the gene function research.This paper discuss three functional areas, and found that these mutations may cause virus antigen expression, vaccine escape, patients condition change, etc., so should strengthen the monitoring in patients with these mutations.

【Abstract】To investigate the molecular characteristics of the hepatitis B virus (HBV) genome in chronic HBV-infected patients in Fujian Province of China, serum samples were collected from patients with chronic HBV infection. HBV DNA was extracted for amplification of surface genes, basic core promoter (BCP) genes and precore (Pre-C) genes amplification. Polymerase chain reaction (PCR) products were sequenced and compared with standard sequences in GenBank. Sequencher, MEGA5 and Bioedit were used for mutation analyses of the HBV genome. We obtained 82 complete sequences of HBV. In all sequences, 56 were B genotype and 26 were C genotype. Gene sequencing revealed that these HBV gene sequences in S (23.2%), BCP (61.0%) and Pre-C (29.3%) regions had a different degree of variation. The frequency of a determinant amino acid (aa) variant was 45. 8%. Those mutation sites might be correlated with severe liver diseases and immune escape, such as the sites of aa126, aa129 and aa145. Analyses revealed that site G1896A (19.5%), G1764A (11.0%) and A1762T (9.8%) remained the major mutations in the BCP/Pre-C region. Simultaneously, the high mutation rate of A1752G (25.6%) in BCP merited attention. G1764A (χ2 = 6.498, P = 0.013), A1896G (10.444, 0.001) and A1762T/G1764A) mutations were more likely to occur in HBeAg–negative samples. A1846T (χ2 = 11.882, P = 0.003), A1762T (6.561, 0.038) and A1896G (6.958, 0.030) mutations had some relevances with HBV DNA load. In conclusion, people with chronic HBV infection in Fujian Province of China had different degrees of variation in HBV gene-function areas. Some of these mutations were associated with HBeAg expression, HBV DNA load, immune evasion of vaccines, and occurrence of hepatocellular carcinoma. Patients with these mutations need strengthened monitoring.

【Keywords】 Hepatitis B virus (HBV) ; Genetic mutations; Basic core promoter (BCP) ; Pre-C region;


【Funds】 National Science and Technology Major Project of China (No. 2012ZX10002001-002-002) National Science and Technology Major Project of China (No. 2017ZX10103008-004)

Download this article


    [1] Hunt C M, Mcgill J M, Allen M I, Condreay L D. Clinical relevance of hepatitis b viral mutations [J]. Hepatology, 2000, 31(5): 1037–1044.

    [2] Park Y M, Jang J W, Yoo S H, Kim S H, Oh I M, Park S J, Jang Y S, Lee S J. Combinations of eight key mutations in the X/preC region and genomic activity of hepatitis B virus are associated with hepatocellular carcinoma [J]. J Viral Hepat, 2014, 21(3): 171–177.

    [3] Chook J B, Teo W L, Ngeow Y F, Tee K K, Ng K P, Mohamed R. Universal primers for detection and sequencing of hepatitis B virus genomes across genotypes A to G [J]. J Clin Microbiol, 2015, 53(6): 1831–1835.

    [4] Qian F C, Qin J Q, Yang S X, Wang X, Dai L C. Surface gene variants of hepatitis B virus in patients with chronic HBV infection [J]. Chinese Journal of Nosocomiology, 2011, 21(8): 1514–1516 (in Chinese).

    [5] Chen F L, Chen L P, Ai Y C, Cheng J L. Chinese Journal of Infectious Diseases, 2016, 34(6): 382–384 (in Chinese).

    [6] Coppola N, Onorato L, Minichini C, Di C G, Starace M, Sagnelli C, Sagnelli E. Clinical significance of hepatitis B surface antigen mutants [J]. World J Hepatol, 2015, 7(27): 2729–2739.

    [7] Yao Q L, Liu J H. 乙型肝炎病毒基因变异的研究进展 [J]. Chinese Journal of Nosocomiology, 2010, 20(18): 2895–2897 (in Chinese).

    [8] Ma Q, Wang Y F. Comprehensive analysis of the prevalence of hepatitis b virus escape mutations in the major hydrophilic region of surface antigen [J]. J Med Virol, 2012, 84(2): 198–206.

    [9] Guo Y H, Feng D X, Dong P M, Zhang S, Xu J, Zhang Y Y, Wang Z. Analysis on Genotype distribution and mutation of major hydroponic region of hepatitis B virus in Henan province [J]. Chinese Journal of Virology, 2017, 33(1): 44–48 (in Chinese).

    [10] Chen J H, Liu Y, Xu Z H, Si L L, Dai J Z, Li Q, Wang S, Li J, Han J Q. Characteristics of S gene mutation in patients with occult HBV infection [J]. Medical Journal of Chinese People’s Liberation Army, 2015, 3(40): 178–183 (in Chinese).

    [11] Romina S, Luna C, Maria C B, Matteo S, Christina B, Claudia A, Marianna A, Alessandra R, Daniele A, Michela P, Fabiola D S, Luca C, Yoram L, Claudio MM, Miriam L, Maurizio P, Mariarosaria E, Chiara D'A, Aldo M, Massimo M, Cesare S, Loredana S, Massimo A, Mario A, Jens V, Carlo-F P, Valentina S. Hepatitis b surface antigen genetic elements critical for immune escape correlate with hepatitis B virus reactivation upon immunosuppression [J]. Hepatology, 2015, 61(3): 823–833.

    [12] Liu S L, Dong Y, Zhang L, Li M W, Wo J, Lu L W, Chen Z J, Wang Y Z, Ruan B. Influence of hbv gene heterogeneity on the failure of immunization with hbv vaccines in eastern China [J]. Arch Virol, 2009, 154(3): 437–443.

    [13] Bouchra K, Abdellah E E F, Rajaa A, Christian T, Mustapha B, Wafaa E, Fabien Z, Isabelle C, Hanane S A, Sayeh E, Soumaya B. Variability in the precore and core promoterregions of hbv strains in Morocco: Characterization and impact on liver disease progression [J/OL]. PLoS One, 2012, 7(8): e42891.

    [14] Soad G, Zohreh S, Seyed M H, Mahmood M S. Correlation between viral load of hbv in chronic hepatitis b patients and precore and basal core promoter mutations [J/OL]. Hepat Mon, 2012, 13(2): e7415.

    [15] Huang Y, Deng H J, Shan X F, Gong X Y, Li X S, Tu Z, Long Q X, Huang A L. Lower mutation frequency of BCP/precore regions in e antigen-negative chronic hbv-infected children instead of adults patients [J/OL]. PLoS One, 2015, 10(3): e0120733.

    [16] Yu W H, Zhang C L, Feng Y L, Zhou D Q, He J S, Zhou X M, Li W X, Chen X H, Lin Z L, Deng J L. Study on the relationship between precore and BCP mutants and hepatitis B virus genotyping in patients with HBV infection [J]. Chinese Journal of Clinicians (Electronic Edition), 2011, 5(12): 3464–3468 (in Chinese).

    [17] Yan J, Yao Z, Hu K, Zhong Y, Li M, Xiong Z, Deng M. Hepatitis B virus core promoter A1762T/G1764A(TA)/T1753A/T1768A mutations contribute to hepatocarcinogenesis by deregulating Skp2and P53 [J]. Dig Dis Sci, 2015, 60: 1315–1324.

    [18] Zhang H R, Sun M, Liu X Y, Zhao W, Cao L, Li M. The mutations in the core promoter and the precore gene of hepatitis B virus in patients with chronic hepatitis B positive for anti–HBe [J]. Journal of Clinical Hepatology, 2005, 21(14–16) (in Chinese).

    [19] Shu Y, Wang W, Dai P, Zhang W T, Cheng S, Li D, Ji Q F, Qiu R H, Liu H L, Zhao W L, Yan Z. Analyses of the Genetic Diversities and Mutations of the hepatitis B virus genome BCP/Pre C region [J]. Chinese Journal of Virology, 2017, 33(1): 36–43 (in Chinese).

    [20] Zhang D K, Ma S F, Zhang X, Zhao H Q, Ding H G, Zeng C Q, Ding H G. Prevalent hbv point mutations and mutation combinations at BCP/preC region and their association with liver disease progression [J]. BMC Infect Dis, 2010, 10: 271.

    [21] Chen Y X, Li X F, Lou L Q, Zhu J H, Jing L Z, Fu Q Y, Zheng Y, Chen Y P. Relationship between hepatitis B e antigen and hepatitis B virus precore/basic core promoter mutation in patients with hepatocellular carcinoma [J]. Chinese Journal of Nosocomiology, 2012, 22(23): 5208–5210 (in Chinese).

    [22] Zhand S, Karami C, Hosseinzadeh A A, Tabarraei A, Khodabakhshi B, Moradi A. Correlation between hepatitis b G1896A precore mutations and HBeAg in chronic hbv patients [J/OL]. Jundishapur J Microbiol, 2015, 8(2): e17126.

This Article



Vol 34, No. 04, Pages 491-497

June 2018


Article Outline



  • Materials and methods
  • Results
  • Discussion
  • References