耐阿德福韦酯乙型肝炎病毒多聚酶区基因突变模式与病毒B、C基因型相关性分析

Relationship between HBV polymerase gene mutations and B, C genotypes in adefovir dipivoxil- resistant chronic hepatitis B patients

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-P25）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rtA181V／T／s突变模式为主，占65．59％（61／93）；HBVB基因和C基因rtA181V／T／S和rtN236T突变模式比较差异均有统计学意义（χ2=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 Febnaary 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 （χ2 = 12. 269, P 〈 0. 01 ） and rtN236T （χ2 = 18. 658, P 〈 0.01 ） mutation rates between B and C genotypes were statistically significant. Conclusion rtA181V/T/S, rtN236T and rtAI81V/T/S ＋ rtN236T are the major HBV polymerase gene mutation types in ADV resistant CHB patients, and mutation types are related with HBV genotypes.