乙型肝炎病毒Y（I/V）DD变异与前C及C基因启动子变异生物信息研究  

Relationship between hepatitis B virus polymerase gene mutation patterns of rtM204I/V and pre-core/basal core promoter mutations

作　　者：阎丽[1] 王介飞 王战会[2] 孙剑[2] 周彬[2] 侯金林[2] 

机构地区：[1]上海复旦大学附属公共卫生临床中心肝病中心,200083 [2]南方医科大学南方医院感染科

出　　处：《中华肝脏病杂志》2014年第12期891-894,共4页Chinese Journal of Hepatology

摘　　要：目的 分析HBV反转录酶区（RT）rtM204位点Y（I/V）DD变异与前C及C基因启动子（PC-BCP）变异关系. 方法 应用MEGA4对来自GenBank/EMBL/DDBJ的人类2 849株HBV全基因序列序列重新排列,分析Y（I/V）DD变异与PC-BCP变异及模式相关性. 结果 rtM204（I/V）DD变异株217株（8.0％）; PC-BCP变异株1 543株（54.2％）,有（1）G1896A、（2）G 1899A、（3） G1896A＋G1899A、（4） A1762T/G1764A、（5） A1762T/G1764A＋G1896A、（6）A 1762T/G 1764A＋G1899A、（7） A1762T/G1764A＋G1896A＋G1899A 7种变异模式; Y（I/V）DD与PC-BCP联合变异165株.YMDD与PC-BCP双变异率高于单纯YMDD变异率（76％比24.0％,x^2=45.283,P=0.000）;YIDD与PC-BCP双变异率高于YVDD与PC-BCP双变异率（85％比64.9％,x^2=11.836,P=0.000）及使用LAM致YMDD与PC-BCP双变异率高于未使用LAM预存YMDD与PC-BCP双变异率（89.3％比58.9％,x2=27.084,P=0.000）.二分类logistic回归分析仅对YIDD有影响而对YVDD无影响的PC-BCP变异模式有G1896A-G1899A（P=0.000,OR=7.573）、A1762T/G1764A-G1899A（P=0.000,OR=6.539）和A1762T/G 1764A-G 1896A-G1899A（P=0.000,OR=6.596）. 结论 YMDD变异与PC-BCP变异相关;PC-BCP变异模式的差异与YI/VDD变异选择强度有一定的关系.Objective To investigate the relationship between mutations of rtM204V/I （methionine to valine or isoleucine at position rt204 of reverse transcriptase domain） in the hepatitis B virus （HBV） polymerase gene and the G1896A and G1899A single mutations in the pre-eore （PC） region and the A1762T and G1764A double-mutations in the basal core promoter （BCP） region.Methods A total of 2,849 hepatitis B complete genome sequences were retrieved from the GenBank/EMBL/DDBJ.The amino acid sequence of the of reverse transcriptase domain and genome sequences of the PC region and the BCP region were aligned using MEGA4 software.Data were calculated using Microsoft Excel and evaluated using SPSS 13.0 statistical software.Results Among the 2,849 HBV complete genome sequences,217 （8%） strains were identified with Y（I/V） DD and 120 of those had the YIDD mutation and 97 had the YVDD mutation.Of the 1543 strains （54.2%） with PC-BCP mutations,seven mutation patterns of G 1896A-G 1899A-G 1896A-G 1899A-A 1762T/G 1764A,A 1762T/G 1764AG 1896A,A 1762T/G 1764A-G 1899A,and A 1762T/G 1764A-G 1896A-G 1899A were identified.of YMDD and PC-BCP had a higher incidence than the single YMDD mutation （76% vs 24.0%,x2 =45.283,P =0.000）.The double-mutations of YIDD and PC-BCP had a higher incidence than the double-mutation of YVDD and PC-BCP （85% vs 64.9%,x2 =11.836,P=0.000）.The double-mutation for lamivudine resistance of YMDD and PC-BCP had a higher incidence than the double pre-existent YMDD and PC-BCP mutations （89.3% vs 58.9%,x^2 =27.084,P =0.000）.The three mutation patterns of G1896A-G1899A （P =0.000,OR =7.573）,A1762T/G1764A-G1899A （P =0.000,OR =6.539） and A1762T/G1764A-G1896A-G1899A （P =0.000,OR =6.596） were associated with a greater risk of developing the YIDD mutation,according to binary logistic analysis.Conclusion There is a relationship between the HBV YI/VDD mutation and PC-BCP mutations.Different PC-BCP mutation patterns have different effects on the YI/VDD mutation.Among the Y（I/V）DD

关 键 词：肝炎病毒 乙型 基因型 变异 

分 类 号：R373.21[医药卫生—病原生物学]