拉米夫定耐药株感染者基因型、HBV DNA及多聚酶P区基因变异的关系

目的分析拉米夫定耐药株感染者的基因型、HBVDNA及多聚酶P区基因变异的关系。方法应用PCR扩增和直接测序法检测83例拉米夫定耐药患者HBV基因型、HBVDNA及多聚酶P区的基因变异。结果83例拉米夫定耐药患者B基因型26例，C基因型57例，B型YIDD变异率69．2％（18／26）、YVDD变异率30．8％（8／26），C型YIDD变异率63．2％（36／57）、YVDD变异率33．3％（19／57），B、c基因型发生YMDD变异模式无统计学差异（P〉0．05）；B型rtM204I突变率53．8％（14／26），综合变异率46．2％（12／26），C型rtM2041变异率26．7％（15／57），综合变异率73．7％（42／57），B、C基因型变异位点类型有统计学差异（P〈0．05）；耐药变异时c型HBVDNA水平（6．60±1．42）lg拷贝／毫升高于B型（5．88±1．46）1g拷贝／毫升，YIDD变异时c型（6．40±1．48）lg拷贝／毫升、B型（5．68±1．32）1g拷贝／毫升，YVDD变异时C型（6．18±1．87）1g拷贝／毫升、B型（6．82±1．45）lg拷贝／毫升；rtM204I变异时B型（6．12±1．45）lg拷贝／毫升、C型（5．57±1．45）lg拷贝／毫升（P〉0．05）；综合变异时c型（6．68±1．51）lg拷贝／毫升，B型（5．76±1．57）lg拷贝／毫升（P〈0．05）。结论c基因型拉米夫定耐药发生率高于B型；基因型与变异位点类型有关，与YMDD变异模式无关；耐药变异时HBVDNA水平c型高于B型，与综合变异有关，与YMDD变异模式无关。

Polymerase Region Mutations,Hepatitis B Virus Genotypes and HBV DNA in Chronic Hepatitis B Patients with Lamivudine - resistant HBV Infection

Objective To analyze the HBV DNA, mutation patterns of Polymerase region and genotype in patients with lamivudine - resistant HBV infection. Methods Serum samples were collected from 83 hepatitis B patients resistant to lamivudine. HBV P gene was amplified by PCR. The PCR products were detected for the genotypes, polymerase region mutations sites and viral loads directly. Results In 83 cases with 1 amivudine -resistant HBV infection, 26 （31.33% ） were infected with genotype B and 57 （68.67%） with genotype C. 18 patients with HBV genotype B and 36 patients with genotype C developed YIDD mutations （69.2% vs 63.2% ）. Meanwhile, 8 pa- tients with genotype B and 19 patients with genotype C developed YVDD mutations （30.8% vs 33.3% ） , therefore, genotype B and C de- veloped YMDD mutations had no significant difference（P 〉0.05）. Regard to site mutation, the genotype B developed rtM204I mutation rate（53.8% ） was higher than genotype C （26.7%） and genotype C multi - site mutation rate （73.7%） was higher than genotype B （46.2%） ,and the result was significant difference （P 〈0.05）. When HBV have mutated,the levels of HBV DNA in genotype C were higher than those in genotype B [ （5.88 ＋ 1.46） lg copies/ml vs （6.60 ＋ 1.42） lg eopies/ml, respectively, P 〈 0.05 ） ]. It had no relation to YMDD mutation [YIDD mutation （6.40~1.48） vs （5.68 ~l.32）,P〉O.05],YVDD mutation[（6.82 ＋1.45） vs （6.18 1.87） , P〉0.051.But it had relation to site mutation（rtM204I mutation [（6. 12 1.45） vs （5.57 1.45）,P〉0.05],multi-site mutation type C[（6.68 ＋1.51） vs （5.76 ＋1.57） ,P〈O.051. Conclusion The incidence oflamivudine-resistance in genotype C was higher than in type B. YMDD mutation had no relation to genotypes. Sites mutation was associated with genotypes. The levels of HBV DNA was higher than that in C type. It was related to the multi - site mutation, but had nothing to do with YMDD mutation.