核苷(酸)类似物治疗慢性乙型肝炎多位点耐药基因的检测

Significance of detection of nucleotide-resistance gene mutation in patients with chronic hepatitis B

目的探讨核苷(酸)类似物治疗的乙肝患者多位点耐药基因突变与临床意义。方法对30例临床耐核苷酸类似物治疗的乙肝患者,分别从血清中提取HBV DNA,进行PCR和DNA直接测序,并进行单核苷酸多态性(SNP)分析判断有无变异及变异模式。结果 30例中有17例发生不同位点变异,变异率为56.67%,另有5例经DNA测序可见碱基突变,但未见明显耐药基因。常见基因变异模式依次为M204I、L180M、A181T、L180M+M204I+V173L、L180M+M204I/V、L180M+M204V+T184I,6种突变模式与ALT、HBV、DNA之间的关系差异无统计学意义(P>0.05)。结论检测HBV多位点耐药基因相关突变有助于临床及时发现乙肝患者HBV耐药并指导临床用药。

Objective To explore the significance of nucleotide- resistance gene mutation in patients with chronichepatitis B. Methods HBV DNA from the serum of 30 patients with hepatitis B received necleotide analogues therapy wereextracted, sequenced by PCR and direct DNA sequencing and then analyzed by single nuleotide polymorphism（SNP） to detectthe variation and variation pattern. Results Gene variation was detected in 17 of 30（56.67%）patients, base mutation wasfound in 5 cases by DNA sequencing, and no drug-resistance gene was found.The common genetic variation patterns wereM204I, L180M, A181T, L180M＋M204I＋V173L, L180M＋M204I/V, L180M＋M204V＋T184I, respectively. There was nosignificant difference between the six genetic variation patterns and ALT, HBV DNA（P〈0.05）. Conclusion Detection ofpolymorphism in multidrug-resistance gene variation helps find drug-resistance in patients with chronic hepatitis B and guidethe clinical medication