基因芯片技术对乙型肝炎病毒拉米夫定耐药基因变异检测的临床应用

Clinical application of microarray technique to quantify the lamivudine-resistant gene mutant of hepatitis B virus

目的通过对应用拉米夫定治疗患者HBV基因耐药性变异的长期监测，验证基因芯片技术的临床应用前景。方法针对HBV3个主要的拉米夫定耐药性相关突变设计探针，制成HBV耐药寡核苷酸芯片，选取51例应用拉米夫定进行治疗的乙型肝炎患者分别采用基因芯片和传统测序的方法对其进行24个月的监测，观察HBV基因变异情况。结果39％的患者在用药2年内发生了耐药性突变，使用基因芯片与传统的测序方法得到的结果一致，并且可以在早期方便检测出混合感染。结论应用基因芯片技术可以准确，高效的检测出耐药基因变异，具有临床应用价值。

Objective To evaluate clinical applicability of a novel technique that can quantify the lamivudine-resistant mutants of hepatitis B virus （HBV） in the serum of patients utilizing gene microarray technology. Methods The oligonucleotide microarray was designed to detect 3 important mutational positions. Fifty-one patients who were receiving lamivudine therapy were selected as subjects. The oligonucleotide microarray and traditional sequcing were applied to detect the lamivudine resistant mutation, the monitoring lasted for 24 months. Then the clinical result was analyzed and the obtained data were compared between the two methods. Results Lamivudine resistant mutation was detected in 39 % of the patients during the 2 years period. The results of the oligonucleotide microarray technique was consistent to the results of traditional sequencing in accuracy and the miroarray was more sensitive in detection of the mixed infection. Conclusion Application of the oligonucleotide microarray for quantitative detection of lamivudine-resistant mutation of HBV is feasible.