title: Mutations in pre-core and basic core promoter regions of hepatitis B virus in chronic hepatitis B patients.
abstract: OBJECTIVE
  To investigate the frequency of mutations in pre-core (pre-C) and basic core promoter (BCP) regions of hepatitis B virus (HBV) from Shanxi Province, and the association between mutations and disease related indexes.
  
  
  METHODS
  One hundred chronic hepatitis B patients treated at Shanxi Province Hospital of Traditional Chinese Medicine were included in this study. PCR-reverse dot blot hybridization and mismatch amplification mutation assay (MAMA)-PCR were used to detect the mutations in the HBV pre-C and BCP regions. HBV DNA content and liver function were compared between patients with mutant HBV pre-C and BCP loci and those with wild-type loci. The consistency between PCR-reverse dot blot hybridization and MAMA-PCR for detecting mutations in the HBV pre-C and BCP regions was assessed.
  
  
  RESULTS
  Of the 100 serum samples detected, 9.38% had single mutations in the pre-C region, 29.17% had single mutations in the BCP region, 41.67% had mutations in both BCP and pre-C regions, and 19.79% had wild-type loci. The rates of BCP and pre-C mutations were 65.7% and 34.3%, respectively, in hepatitis B e antigen (HBeAg) positive patients, and 84.6% and 96.2%, respectively, in HBeAg negative patients. The rate of pre-C mutations was significantly higher in HBeAg negative patients than in HBeAg positive patients (χ (2) = 26.62, P = 0.00), but there was no significant difference in the distribution of mutations in the BCP region between HBeAg positive and negative patients (χ (2) = 2.43, P = 0.12). The presence of mutations in the pre-C (Wilcoxon W = 1802.5, P = 0.00) and BCP regions (Wilcoxon W = 2906.5, P = 0.00) was more common in patients with low HBV DNA content. Both AST and GGT were significantly higher in patients with mutant pre-C and BCP loci than in those with wild-type loci (P < 0.05). PCR-reverse dot blot hybridization and MAMA-PCR for detection of mutations in the BCP and pre-C regions had good consistency, and the Kappa values obtained were 0.91 and 0.58, respectively.
  
  
  CONCLUSIONS
  HBeAg negative patients tend to have HBV pre-C mutations. However, these mutations do not cause increased DNA copies, but associate with damage of liver function.
authors.affiliation: Xiao-Ling Wang, Jian-Ping Ren, Xue-Qing Wang, Xiao-Hong Wang, Shao-Fang Yang, Yi Xiong, Department of Clinical Laboratory, Shanxi Provincial Hospital of Traditional Chinese Medicine, Taiyuan 030012, Shanxi Province, China.
authors.forename: Xiao-Ling
authors.initials: XL
authors.lastname: Wang
authors.affiliation: Xiao-Ling Wang, Jian-Ping Ren, Xue-Qing Wang, Xiao-Hong Wang, Shao-Fang Yang, Yi Xiong, Department of Clinical Laboratory, Shanxi Provincial Hospital of Traditional Chinese Medicine, Taiyuan 030012, Shanxi Province, China.
authors.forename: Jian-Ping
authors.initials: JP
authors.lastname: Ren
authors.affiliation: Xiao-Ling Wang, Jian-Ping Ren, Xue-Qing Wang, Xiao-Hong Wang, Shao-Fang Yang, Yi Xiong, Department of Clinical Laboratory, Shanxi Provincial Hospital of Traditional Chinese Medicine, Taiyuan 030012, Shanxi Province, China.
authors.forename: Xue-Qing
authors.initials: XQ
authors.lastname: Wang
authors.affiliation: Xiao-Ling Wang, Jian-Ping Ren, Xue-Qing Wang, Xiao-Hong Wang, Shao-Fang Yang, Yi Xiong, Department of Clinical Laboratory, Shanxi Provincial Hospital of Traditional Chinese Medicine, Taiyuan 030012, Shanxi Province, China.
authors.forename: Xiao-Hong
authors.initials: XH
authors.lastname: Wang
authors.affiliation: Xiao-Ling Wang, Jian-Ping Ren, Xue-Qing Wang, Xiao-Hong Wang, Shao-Fang Yang, Yi Xiong, Department of Clinical Laboratory, Shanxi Provincial Hospital of Traditional Chinese Medicine, Taiyuan 030012, Shanxi Province, China.
authors.forename: Shao-Fang
authors.initials: SF
authors.lastname: Yang
authors.affiliation: Xiao-Ling Wang, Jian-Ping Ren, Xue-Qing Wang, Xiao-Hong Wang, Shao-Fang Yang, Yi Xiong, Department of Clinical Laboratory, Shanxi Provincial Hospital of Traditional Chinese Medicine, Taiyuan 030012, Shanxi Province, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Xiong
mesh_terms: D000328:Adult; D016009:Chi-Square Distribution; D004252:DNA Mutational Analysis / Q000379:methods; D004279:DNA, Viral / Q000235:genetics*; D005260:Female; D005838:Genotype; D006512:Hepatitis B Core Antigens; D006513:Hepatitis B e Antigens / Q000097:blood; D006515:Hepatitis B virus / Q000235:genetics* / Q000276:immunology; D019694:Hepatitis B, Chronic / Q000097:blood / Q000175:diagnosis / Q000821:virology*; D006801:Humans; D008111:Liver Function Tests; D008297:Male; D008875:Middle Aged; D009154:Mutation; D016133:Polymerase Chain Reaction / Q000379:methods; D011401:Promoter Regions, Genetic; D014758:Viral Core Proteins / Q000235:genetics*; D055815:Young Adult
chemical_list: D004279:DNA, Viral; D006512:Hepatitis B Core Antigens; D006513:Hepatitis B e Antigens; D014758:Viral Core Proteins
keywords: Basic core promoter region; Liver injury; Mismatch amplification mutation assay; Pre-core region; Reverse dot blot hybridization