目的 分析耐阿德福韦酯(ADV)慢性乙型肝炎(CHB)患者中HBV多聚酶区基因突变模式及基因型的关系.方法 选取2010年2月-2012年5月宁波市第二医院住院及门诊114例ADV耐药的CHB患者,采用实时荧光定量PCR方法对患者血清HBV多聚酶区进行扩增,对PCR产物进行直接测序比对.正态分布的计量资料以(-x)±s表示,非正态分布数据用M(P25 ～ P75)表示,经过数据转换方差齐的采用方差分析和LSD-t检验.结果 114例CHB患者的基因突变模式为8种,以rtA181V/T/S(57.89％)、rtN236T(14.91％)和rtA181V/T/S+ N236T(9.65％)突变为主,其中单独突变102例(89.47％),联合突变12例(10.53％).114例患者B基因和C基因分别为21例(18.42％)和93例(81.58％),B基因以rtN236T突变模式为主,占47.62％(10/21)；C基因以rtA181 V/T/S突变模式为主,占65.59％ (61/93)；HBV B基因和C基因rtA 181V/T/S和rtN236T突变模式比较差异均有统计学意义(x2=12.269和18.658,P＜0.01).结论 耐ADV的CHB患者血清HBV多聚酶区基因突变以rtA181V/T/S、rtN236T和rtA181V/T/S+ N236T为主,且不同基因突变模式与基因型有关.%Objective To investigate the relationship between HBV polymerase gene mutations and HBV genotypes in chronic hepatitis B (CHB) patients resistant to adefovir dipivoxil (ADV).Methods Blood samples were collected from 114 ADV-resistant CHB patients during February 2010 and May 2012.The HBV polymerase regions from serum samples were amplified with real-time PCR,and the PCR products were sequenced.Normal distribution data were presented as x ± s,and non-normal distribution data were presented as M (P25-P75) ; for homogeneous data analysis of variance and LSD-t test were performed.Results There were 8 types of HBV polymerase gene mutations in 114 CHB patients; single point mutation was detected in 102 patients (89.47％) and double or triple points mutations were detected in 12 patients (10.53％).rtA181V/T/S (57.89％),rtN236T (14.91％) and rtA181V/T/S + N236T (9.65％) were the predominant mutations.For 21 patients (18.42％) with HBV genotype B,rtN236T mutation was prevalent (47.62％,10/21) ; while for those with HBV genotype C (93,81.58％),rtA181V/T/S mutation was the predominant (65.59％,61/93).The differences of rtA181V/T/S (x2 =12.269,P ＜0.01) and rtN236T (x2 =18.658,P ＜0.01) mutation rates between B and C genotypes were statistically significant.Conclusion rtA181V/T/S,rtN236T and rtA181V/T/S + rtN236T are the major HBV polymerase gene mutation types in ADV resistant CHB patients,and mutation types are related with HBV genotypes.
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