基因芯片检测慢性乙肝患者HBV-DNA变异的临床研究

目的应用新型基因芯片研究乙肝病毒多点基因变异在慢性乙肝患者中的意义，为临床诊断和治疗提供依据。方法对132例慢性乙肝患者采用DNA芯片技术，检测HBV—DNA基因6个位点的变异。结果132例慢性乙型肝炎患者均存在HBV—DNA位点的变异，其中前C区1896G—A变异率为23．5％。e抗原阳性者占4．O％（4／74）。e抗体阳性者占48．3％（28／58），后者变异株显著高于前者，此突变有助于HBV逃避免疫攻击而形成慢性感染状态；前C区1814变异率为3．8％；C区启动子1762变异率为56．1％，1764变异率为53．8％，且两种变异常同时出现，与重型肝炎、肝硬化和肝癌的发生相关；P区528变异率为9．8％，552M—I变异率38．6％，552M—V变异率为10．6％，552变异与核苷类似物耐药相关。结论HBV—DNA位点变异对于判定疾病的稳定与进展有重要作用。

Clinical Study of Genechip Detecting HBV-DNA Polymorphism

Objective To study clinical significance of DNA chip technique in detecting the mutation of HBV- DNA ORF, and to offer testimony for clinical diagnosis and treatment. Methods Gene sequence of hepatitis B virus DNA and mutations of 6 sites in serum of 132 aniso-type patients were detected by DNA chip technique. Results The mutations of HBV-DNA ORF existed in all 132 patients. The rates of mutation on Pre-C 1896, Pre- C1814, BCP1762, P528, P552M-1, P552M-V were 23.5%, 4%, 56.1%, 53.8%, 9.8%, 38.6%,10.6% respectively. The mutation rate of Pre-C1896 was 4.0% in the patients with HBeAg positive and 48.3% in the patients with HBeAb positive. There was significant difference between the latter and the former. The mutations on Pre-C 1896 helped HBV escape from immune assault and develop chronic infection. The mutation of 1762 and 1764 always occurred together, and was related to occurrence of carcinoma and severe hepatitis. The mutation of 552 was related to drug resistance of lamivudine. Conclusion The mutation of HBV-DNA site has important influence on predicting the stability and progress of the disease.