黑龙江地区400例乙型肝炎病毒基因分型与耐药突变研究

Research of Hepatitis B virus Genotyping and Variation of Drug Resistance in 400 Cases in Heilongjiang Area

目的:运用基因芯片技术分析黑龙江地区乙型肝炎病毒(HBV)基因型分布特征及基因耐药变异情况。方法:随机选择2012年11月至2015年11月本医院乙型肝炎患者血清样本400例,应用PCR-反向点杂交的基因芯片技术对样本血清中HBV基因型及常见4类抗病毒药物耐药相关的多个位点进行检测,并进行数据分析。结果:400例样本中基因型分布以C型为主占83.25%(333例),B型7.25%(29例)、D型0.25%(1例)及混合基因型2.75%(11例);耐药突变位点检出188例,总耐药率为45.19%,其中突变位点236T(4.61%)提示阿德福韦酯单项耐药,耐药率为5.82%(10例),与拉米夫定耐药相关的为126例,突变位点以rt204I和(rt180M+rt240V)为主,显著高于其他抗病毒类药物,耐药风险较高。结论:黑龙江地区乙型肝炎基因分型以C为主,B型和其它混合型较少,且更容易对拉米夫定产生耐药。

Objective： To investigate the distribution characteristics of hepatitis B virus（HBV） genotypes and the variation situation of drug resistance gene in Heilongjiang area by the gene chip technology. Methods： Serum samples were randomly collected from400 patients of hepatitis B in our hospital from November 2012 to November 2015. The HBV genotypes and drug resistance associated multiple sites in common 4 types of antiviral drug were detected by the gene chip technology of PCR combined with reverse dot blot. Results：Among 400 samples in Heilongjiang area,83.25 % genotypes were genotype C（333 cases）,type B 7.25 %（29 cases）,type D 0.25 %（1case） and mixed type 2.75 %（11 cases）; 188 sites were found to be resistance mutants,the total resistance frequency was 45.19 %,rt236 T mutations in 10 samples prompted drug resistance-mutations for Adefovir drug,and the resistance frequency was 5.82 %,and 126 samples drugs resistance-mutations was Lamivudine drug in major of rt204 I and（rt180M＋rt204V）. 126 cases were related with Lamivudine resistance,which was significantly higher than other antiviral drugs,the risk of drug resistance was greater. Conclusions： The main HBV genotype is the genotype C in Heilongjiang area,genotype B and mixed genotype are unusual,which is more likely to happen resistance to Lamivudine.