基因芯片高通量检测乙型肝炎病毒拉米夫定耐药株及对其突变热点的分析

目的 通过大规模、多位点检测深圳地区拉米夫定耐药株，进一步了解拉米夫定耐药突变的各种分布状况。方法 用基因芯片法对552份乙型肝炎患者血清进行检测，得出l92份拉米夫定耐药突变标本，再对192份耐药标本检测结果进行分析。结果 192份耐药标本中，191份YMDD突变，124份528位点突变，9份555位点突变。YMDD突变中88％为：YVDD、528位点同时突变；YIDD单独突变；YIDD、528位点同时突变。YMDD突变密码子91％为：GTG、ATT；9％为：ATA、ATC。结论 552位点(YMDD)突变为核心突变，528、555位点的突变为协同突变。YVDD突变总是与528位点同时出现；YIDD突变则表现为多样化。YMDD突变密码子约有9％为少见密码子ATA、ATC，这可能是传统聚合酶链反应法检测YMDD突变阳性率较低的原因。

High-flux detection of HBV lamivudine resistant strains by genechip and analysis of mutant hotspots in those strains

Objective Lamivudine resistant HBV strains in Shenzhen were detected at multiple sites and in large amounts to understand further the distribution of lamivudine resistant mutants. Methods 552 Hepatitis B patients' sera were examined using genechip method. Among them, 192 samples of lamivudine resistant mutant were further analyzed. Results In those 192 lamivudine resistant samples, 191 were YMDD mutants, 124 mutants of codon 528 and 9 mutants of codon 555. 88% YMDD mutants were multi-mutants of YVDD and codon 528; single mutants of YIDD; multi-mutants of YIDD and codon 528. 91% codon of YMDD mutants were GTG, ATX; the other 9% were ATA, ATC. Conclusions These results suggest that mutants of codon 552 (YMDD) are core mutants. Mutants of codon 528 and 555 are incidental mutants, YVDD mutants always emerge with mutants of codon 528, but YIDD mutants appear differently. 9% YMDD mutants' codons are ATA or ATC. This may be the reason for the low positive rate shown by using the conventional PCR methods.