title: Male-specific W4P/R mutation in the pre-S1 region of hepatitis B virus, increasing the risk of progression of liver diseases in chronic patients.
abstract: The issue of hepatitis B virus (HBV) mutations possibly leading to a gender disparity in the progression of liver diseases has not been explored. We aimed to elucidate the relationships of the novel pre-S1 mutations, W4P/R, with the progression of liver diseases and male predominance in a South Korean chronic cohort by use of a molecular epidemiologic study. We developed a fluorescence resonance energy transfer (FRET)-based real-time PCR (RT-PCR) assay for the detection of the W4P/R mutations and applied it to 292 chronic HBV patients. The pre-S1 mutations from 247 (84.6%) of a total of 292 patients were detected by this assay. W4P/R mutants were found to be significantly related to severe liver diseases (hepatocellular carcinoma [HCC] and liver cirrhosis, 12.4% [19/153] of patients, versus chronic hepatitis and asymptomatic carriage, 1.1% [1/94] of patients) (P < 0.001). All of the W4P/R mutants were found in males only. The novel HBV pre-S1 mutations, W4P/R, may be associated with disease severity in male patients chronically infected with HBV genotype C. The W4P/R mutations may provide in part an explanation for the relatively high ratio of male to female incidence in HCC generation in South Korean chronic HBV patients.
authors.affiliation: Department of Microbiology and Immunology, Liver Research Institute, Cancer Research Institute and SNUMRC, College of Medicine, Seoul National University, Seoul, South Korea.
authors.forename: Seoung-Ae
authors.initials: SA
authors.lastname: Lee
authors.forename: Ki-Jeong
authors.initials: KJ
authors.lastname: Kim
authors.forename: Dong-Won
authors.initials: DW
authors.lastname: Kim
authors.forename: Bum-Joon
authors.initials: BJ
authors.lastname: Kim
mesh_terms: D000328:Adult; D000368:Aged; D001483:Base Sequence; D004279:DNA, Viral / Q000737:chemistry / Q000235:genetics; D018450:Disease Progression; D005260:Female; D005838:Genotype; D006514:Hepatitis B Surface Antigens / Q000235:genetics*; D006515:Hepatitis B virus / Q000235:genetics* / Q000302:isolation & purification; D019694:Hepatitis B, Chronic / Q000453:epidemiology / Q000473:pathology* / Q000821:virology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D017720:Molecular Epidemiology; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D011498:Protein Precursors / Q000235:genetics*; D056910:Republic of Korea / Q000453:epidemiology; D018570:Risk Assessment; D017422:Sequence Analysis, DNA; D012737:Sex Factors
chemical_list: D004279:DNA, Viral; D006514:Hepatitis B Surface Antigens; D011498:Protein Precursors; C050806:presurface protein 1, hepatitis B surface antigen
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