临汾地区乙型肝炎病毒基因型分布及P区基因耐药突变研究

Analysis of HBV genotypes and mutation patterns of HBV P gene in Linfen

目的了解临汾地区乙型肝炎病毒(HBV)基因型分布以及P区耐药基因位点变异情况。方法对临汾地区2013年1月至2014年12月期间在我院确诊的306例经过不同程度的抗病毒药物治疗的慢性乙型肝炎病毒感染患者中分离得到的HBV株,采用实时定量聚合酶链反应(quantitative real-time PCR)荧光探针法检测其基因型,采用Sanger法对其中60例HBV P区基因序列测定,分析HBV P区基因中17个常见耐药突变位点(rt169-173-180-181-184-202-204-207-213-214-215-229-233-236-237-238-250)的基因突变情况。结果 272例中HBV C型为256例(94.1%),B型为16例(5.9%),无B+C型及其他型;C基因型比B基因型HBV DNA定量值较高(t=6.83,P<0.05);在肝硬化、慢性乙型肝炎组中,C型与B型的分布差异无统计学意义(χ~2=0.067,P>0.05);成功测序的40例HBV P区基因序列中,rtM204V、rtM204Ⅰ和rtN238S均有2例发生突变,且为单个位点突变,突变比例为15.0%(6/40)。结论临汾地区HBV基因型以C型为主;HBV P区基因中17个常见耐药突变位点均为单个位点突变。

Objective To study hepatitis B virus （HBV） genotype distribution and mutation patterns of the P region of HBV gene in Linfen. Methods Realtime quantitative PCR based on fluorescence probe was utilized to detect the genotypes of HBV epidemic strains in Linfen; and the P region of HBV that isolated from 40 patients with chronic HBV infection and with antiviral treatment was sequenced. The most common P area resistance gene mutation sites （rt169-173-180-181-184-202- 204-207-213-214-215-229-233-236-237-238-250） were analyzed. Results Of the HBV strains isolated from 272 patients with chronic hepatitis B, 256 were C genotype （94.1%） and 16 were of B genotype （5.9%）, There was no B＋C genotype and other genotypes. Compared with B genotype, the DNA quantification value of C genotype in clinical specimens was higher（t=6.83, P〈0.05）; but there was no significant difference about the distribution of B/C genotype in the hepatocirrhosis and chronic hepatitis B groups （χ^2 =0.067, P〉0.05）. Among 40 cases, HBV P area gene sequence was successful determinated. There were 2 rtM204V mutations, 2 rtM204I mutations, and 2 rtN238S mutations. All cases of gene mutation were single locus mutation and the mutation rate was 15.0% （6/40）. Conclusions Genotype C is the dominant genotype of HBV in Linfen and only single locus mutations of the P region are detected in this study.