儿童感染乙型肝炎病毒BCP/PC区基因突变特征及其与基因型的关系  

Clinical significance and mutation characteristics in the core promoter/pre-C region of different HBV genotypes in children

作　　者：白俊玺 邓海军 黄勇[3] Bai Junxi;Deng Haijun;Huang Yong(Clinical Laboratory of Dazhou Central Hospital,Dazhou 635000,China;Institute for Viral Hepatitis,Key Laboratory of Molecular Biology for Infectious Diseases,Ministry of Education,Chongqing Medical University,Chongqing 400016,China;Clinical Laboratory of the Second Affiliated Hospital of Chongqing Medical University,Chongqing 400010,China)

机构地区：[1]达州市中心医院检验科,635000 [2]重庆医科大学病毒性肝炎研究所暨感染性疾病分子生物学教育部重点实验室,400016 [3]重庆医科大学附属第二医院检验科,400010

出　　处：《中华肝脏病杂志》2020年第8期667-671,共5页Chinese Journal of Hepatology

摘　　要：目的分析儿童感染乙型肝炎病毒(HBV)基本核心启动子和前C(BCP/PC)区在不同基因型样本中的突变特征及其临床意义。方法收集2011年至2018年期间就诊的294例儿童和92例成人慢性HBV感染患者,PCR扩增HBV BCP/PC区并直接测序,比对分析该区段基因突变情况。两样本均数比较采用t检验,非参数资料的比较采用Wilcoxon-Mann-Whitney检验,两组资料率的比较采用χ^2检验或Fisher精确检验。结果儿童和成人患者均以B基因型为主,分别占76.9%、71.7%,C基因型分别占23.1%、28.3%。在儿童组,nt 1679、1721、1753、1757、1758、1762、1764、1775、1856及1858十个核苷酸位点在C基因型样本中的突变率显著高于B基因型样本,如G1721A、C1856T和T1858C突变在C基因型样本中的突变率分别为30.9%、16.2%和30.9%,而在B基因型样本中的突变率则分别为0.4%、0、0,P<0.001。在成人组,只有nt 1679、1758、1775三个位点在C基因型样本中的突变率显著高于B基因型样本。这些位点多以联合突变的模式被检出,如T1858C突变共检出21例,其中20例为G1721A/A1775G/T1858C三联突变,10例为G1721A/A1775G/C1856T/T1858C四联突变,且这些联合突变模式仅在儿童C基因型样本中被检出,在儿童B基因型及成人样本中均无检出。进一步分析发现,G1721A/A1775G/T1858C三联突变组患者年龄明显低于无突变组患儿[(4.58±2.53)岁对比(6.53±4.02)岁,P=0.012)],血清HBV DNA滴度明显高于无突变组患儿[(7.57±2.03)log10拷贝/ml对比(6.61±2.11)log10拷贝/ml,P=0.045)]。结论儿童感染HBV BCP/PC区在C基因型样本中的突变频率显著高于B基因型样本;与基因型相关的联合位点突变主要见于C基因型儿童样本,且与较低的患者年龄和较高的HBV DNA滴度相关。Objective To understand the clinical significance and mutation characteristics in the basic core promoters and pre-C region(BCP/PC)of different hepatitis B virus genotypes samples of infected children.Methods A total of 294 children and 92 adults with CHB infection who were treated at four hospitals in Chongqing from 2011 to 2018 were collected.The BCP/PC region of HBV was amplified by PCR and sequenced directly to comparatively analyze the gene mutation conditions in this region.The two sample means were compared by the t-test,and the nonparametric data was compared by Wilcoxon-Mann-Whitney test.χ2 test or Fisher's exact test was used to compare the data rates of the two groups.Results Children and adult patients were dominated by genotype B;accounting for 76.9%and 71.7%,respectively,and genotype C accounted for 23.1%and 28.3%,respectively.In the children group,the mutation rates of ten nucleotide sites containing nt 1679,1721,1753,1757,1758,1762,1764,1775,1856 and 1858 of the genotype C samples was significantly higher than that of genotype B samples.The mutation rates of G1721a,C1856t and T1858c of genotype C samples were 30.9%,16.2%and 30.9%,respectively,while the mutation rates of genotype B samples were 0.4%,0,0,P<0.001,respectively.In the adult group,the only three sites containing nt 1679,1758,and 1775 of the genotype C sample had a higher mutation rate than the genotype B samples.The combined mutations pattern were only detected in children with genotype C samples,but not in children and adult with genotype B samples.Further analysis showed that the age of G1721A/A1775G/T1858C containing combined mutation group was significantly lower than that of the non-mutation group[(4.58±2.53)years vs.(6.53±4.02)years,P=0.012].Serum HBV DNA titer was significantly higher in combined mutation group than that of the non-mutation group[(7.57±2.03)log10 copies/ml vs.(6.61±2.11)log10 copies/ml,P=0.045].Conclusion The frequencies of mutations in the BCP/PC region of HBV-infected children in genotype C samples were si

关 键 词：乙型肝炎病毒 基因突变 BCP/PC区 儿童 

分 类 号：R725.1[医药卫生—儿科]