Yin Yuzhu, Zhang Peizhen, Tan Zhangmin, Zhou Jin, Wu Lingling, Hou Hongying
Department of Obstetrics and Gynecology, Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China.
Hepat Mon. 2016 Mar 6;16(3):e32160. doi: 10.5812/hepatmon.32160. eCollection 2016 Mar.
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.
To assess the association of hepatitis B virus (HBV) S gene mutations with vertical transmission.
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.
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.
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.
乙肝病毒（HBV）前S/S基因突变可发生在联合疫苗接种计划实施之前或之后。HBV前S/S基因突变是疫苗接种失败的一个危险因素，并经常导致HBV垂直传播。
评估乙肝病毒（HBV）S基因突变与垂直传播之间的关联。
在这项前瞻性巢式病例对照研究中，共有60例血清HBsAg阳性且HBV DNA≥10⁷IU/mL的孕妇，根据其婴儿HBV感染检测是否呈阳性，分为病例组（15例疫苗接种失败）和对照组（45例疫苗接种成功）。病例组的母亲及其子女进一步细分为母亲、新生儿和婴儿组（7个月大时为同一新生儿）。通过聚合酶链反应（PCR）检测前S/S基因突变并进行测序，分析其与HBV垂直传播的关联。
两组母亲中，HBV B基因型均为主要基因型。病例组中每对母婴具有相同的HBV基因型。病例组和对照组母亲之间，以及病例组母亲、新生儿和婴儿之间，HBV前S/S基因突变频率均无显著差异（片段1（母亲）：2例对4例，P>0.05；片段2（母亲）：10例对10例，P>0.05）。两组母亲的突变位点分析显示，HBV前S/S基因中有108个不同的突变位点，其中105个为沉默突变，5个为错义突变，包括ntA826G、ntC531T、ntT667C、ntC512T和ntC546A。病例组中15对母婴成功进行PCR和测序，其中7对母婴（41.17%）、9对母亲与婴儿（60.00%）和3对婴儿与新生儿（20.00%）的突变位点不同。
疫苗接种失败导致儿童感染HBV是由垂直传播引起的。HBV前S/S基因突变普遍存在，可发生在疫苗接种之前或之后。因此，单纯分析HBV基因突变频率并无价值。为进一步阻断HBV垂直传播，未来研究应关注与疫苗接种失败可能相关的特定突变位点。
