title: The Association of Pre-S/S Gene Mutations and Hepatitis B Virus Vertical Transmission.
abstract: BACKGROUND
  HBV Pre-S/S gene mutations can occur before or after implementation of combined vaccination program. HBV Prs-S/S gene mutation is a risk factor of vaccination failure and frequently causes HBV vertical transfection.
  
  
  OBJECTIVE
  To assess the association of hepatitis B virus (HBV) S gene mutations with vertical transmission.
  
  
  METHODS
  In this prospective nested case-control study, a total of 60 pregnant women with positive serum HBsAg and HBV DNA ≥ 10(7) IU/mL were divided into a case group (15 cases with vaccination failure) and a control group (45 cases with vaccination success) according to whether their infants tested positive for HBV infection. Mothers and their children in the case group were further sub-divided into groups including mothers, newborns and infant (the same newborns at age of seven months). The pre-S/S gene mutations were detected by PCR and sequenced and its association with vertical transmission of HBV was analyzed.
  
  
  RESULTS
  HBV genotype B was the dominant genotype in the both groups' mothers. Each mother-child pair in case group had the same HBV genotype. There were no significant differences in mutation frequencies of HBV Pre-S/S gene between case and control groups' mothers (Fragment 1 (M): 2 vs. 4, P > 0.05; Fragment 2 (M): 10 vs. 10, P > 0.05), or among the mothers, newborns and infants in the case group (Fragment 1 (M): 2, 2, and 3, respectively, P > 0.05; Fragment 2 (M): 10, 10 and 10 respectively, P > 0.05). Mutation site analysis of the both groups' mothers demonstrated 108 different mutation sites in the HBV pre-S/S gene, with 105 silent mutations and 5 missense mutations including ntA826G, ntC531T, ntT667C, ntC512T and ntC546A. Among 15 mother-newborn-infant pairs with successful PCR and sequence in case group, 7 (41.17%) mother-newborn pairs, 9 (60.00%) mother-infant pairs and 3 (20.00%) infant-newborn pairs had different mutation sites.
  
  
  CONCLUSIONS
  HBV in children due to vaccination failure was resulted from vertical transmission. HBV Pre-S/S gene mutations were prevalent and could occur before or after vaccination. Therefore, simply analyzing mutation frequency of HBV gene was not of value. To advance blocking HBV vertical transmission, future studies should focus on specific mutation sites, potentially associated with vaccination failure.
authors.affiliation: Department of Obstetrics and Gynecology, Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China.
authors.forename: Yuzhu
authors.initials: Y
authors.lastname: Yin
authors.affiliation: Department of Obstetrics and Gynecology, Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China.
authors.forename: Peizhen
authors.initials: P
authors.lastname: Zhang
authors.affiliation: Department of Obstetrics and Gynecology, Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China.
authors.forename: Zhangmin
authors.initials: Z
authors.lastname: Tan
authors.affiliation: Department of Obstetrics and Gynecology, Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China.
authors.forename: Jin
authors.initials: J
authors.lastname: Zhou
authors.affiliation: Department of Obstetrics and Gynecology, Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China.
authors.forename: Lingling
authors.initials: L
authors.lastname: Wu
authors.affiliation: Department of Obstetrics and Gynecology, Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China.
authors.forename: Hongying
authors.initials: H
authors.lastname: Hou
keywords: Hepatitis B Virus; Mutation; Pre-S/S; Vaccination Failure