广西HBsAg无症状携带者HBV前S基因缺失突变的分子流行病学研究

Molecular epidemiology of hepatitis B virus pre-S deletion mutations in HBsAg asymptomatic carriers from Guangxi

目的了解广西HBsAg无症状携带者乙肝病毒(HBV)前S基因(PreS)缺失突变株的流行情况。方法按现况研究的原理,用三阶抽样法,在广西东、西、南、北、中各选定1个县,然后在每个县选择人口约1 000人的自然村,调查该村全人群HBV感染情况,用套式聚合酶链反应(nested PCR)对HBsAg阳性血清HBV前S基因扩增和序列分析。结果共调查4 513人,HBsAg总阳性率为8.7%(395/4 513),Pre-S基因缺失突变率为4.9%(17/350),男、女突变率(5.1%、4.5%)无显著性差异(2=0.07,P>0.05),25岁以下没有出现缺失突变,突变率在50岁年龄组最高,但各组间无显著性差异(P>0.05)。汉族人群突变率较高(6%);钦州突变率最高(7.5%),苍梧最低(1.5%),各民族之间、各县之间突变率均无显著性差异(P>0.05)。所有Pre-S缺失突变都是框内突变,82.4%(14/17)的突变发生在或涉及Pre-S2的5’端。Pre-S2起始密码发生突变率为6.9%(24/350)。基因型B、C、I和D前S基因缺失突变率分别为6.1%(7/114)、4.1%(9/221)、7.1%(1/14)和0(0/1),各组间无显著性差异(P>0.05)。结论广西HBV无症状携带者前S基因缺失突变率较低,PreS1的3’端和PreS2的5’端是缺失突变的好发部位,低年龄组罕见,突变与性别、民族、地理位置和基因型无关。

Objectives To understand the molecular epidemiology of hepatitis B virus（HBV） pre-S deletion mutants in HBsAg asymptomatic carriers from Guangxi. Methods According to cross-sectional study and multistage sampling, five counties were selected from eastern, western, northern, southern and central Guangxi. A village with a population of about one thousand was selected from each county. The whole population were surveyed for HBV. The pre-S region of HBV in the sera from those with positive for HBsAg was amplified using nested PCR and sequenced. Results Four thousand five hundred and thirteen individuals were recruited. HBsAg positive rate was 8.7% （395/4513）. The prevalence of pre-S deletions was 4.9% （17/350）. There was not significantly difference in the prevalence of deletions between male and female （5.1% vs. 4.5%）（X2=0.07,P 〉0.05）. No deletion mutation was found in those aged under 25 years old. The mutation rate was highest in the age group of 50 but no significantly difference was found among age groups （P 〉0.05）. The mutation rate was higher in majority Han population（6%）. The highest mutation rate was found in Qinzhou（7.5%） and lowest in Cangwu（1.5%）. No significantly difference was found among ethnic groups, eounties（P 〉0.05）. All of the deletions arc in frame and 82.4% （14/17） of them occurred in or involved the 5＇ terminus of pre-S2. The mutation rate in the pre-S2 initiation codon was 6.9% （24/350）. The deletion rate in genotype B,C,I and D was 6.1% （7/114）,4.1% （9/221）,7.1%（1/14） and 0（0/1）, respectively and nosignificantly difference was found among them（P 〉0.05）. Conclusions The prevalence of HBV pre-S deletion mutations in HBsAg asymptomatic carriers in Guangxi is lower. The 3＇ terminus of the pre-S1 region and 5＇ terminus of the pre-S2 region are the favoured sites for the deletion mutations. The deletion is rare in younger age group. Sex, age, ethnic minority and geographic region are not associated with HBV pre-S deletion mutations.