Naturally occurring precore/core region mutations of hepatitis B virus genotype C related to hepatocellular carcinoma.
Previous studies have proved the presence of several distinct types of mutations in hepatitis B virus (HBV) infections, which are related to the progression of liver disease. However, few reports have detailed the mutation frequencies and mutation patterns in the precore/core (preC/C) region, which are based on the clinical status and HBeAg serostatus. Our aim in this study is to investigate the relationships between the preC/C mutations and clinical severity or HBeAg serostatus from patients chronically infected with HBV genotype C. A total of 70 Korean chronic patients, including 35 with hepatocellular carcinoma (HCC), participated in this study. HBV genotyping and precore/core mutations were analyzed by direct sequencing. All patients were confirmed to have genotype C infections. Mutations in the C region were distributed in a non-random manner. In particular, mutations in the MHC class II restricted region were found to be significantly related to HCC. Six (preC-W28*, C-P5H/L/T, C-E83D, C-I97F/L, C-L100I and C-Q182K/*) and seven types (preC-W28*, preC-G29D, C-D32N/H, C-E43K, C-P50A/H/Y, C-A131G/N/P and C-S181H/P) of mutations in the preC/C region were found to be related to HCC and to affect the HBeAg serostatus, respectively. In conclusion, our data indicated that HBV variants in the C region, particularly in the MHC class II restricted region, may contribute to the progress of HCC in chronic patients infected with genotype C. In addition, we found several distinct preC/C mutations in the Korean chronic cohort, which affect the clinical status of HCC and HBeAg serostatus of patients infected with genotype C.
Department of Microbiology and Immunology, Liver Research Institute and Cancer Research Institute, College of Medicine, Seoul National University, Seoul, Korea.
Dong-Won
DW
Kim
Seoung-Ae
SA
Lee
Eung-Soo
ES
Hwang
Yoon-Hoh
YH
Kook
Bum-Joon
BJ
Kim
D001483:Base Sequence; D006528:Carcinoma, Hepatocellular / Q000503:physiopathology / Q000821:virology*; D016000:Cluster Analysis; D017931:DNA Primers / Q000235:genetics; D005838:Genotype; D006515:Hepatitis B virus / Q000235:genetics*; D006801:Humans; D008113:Liver Neoplasms / Q000503:physiopathology / Q000821:virology*; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D010802:Phylogeny; D056910:Republic of Korea; D017422:Sequence Analysis, DNA; D018709:Statistics, Nonparametric; D014758:Viral Core Proteins / Q000235:genetics*
D017931:DNA Primers; D014758:Viral Core Proteins