慢性乙型肝炎病毒感染者病毒前C区和基本核心启动子区变异检测及意义  

The association of hepatitis B virus precore/basic core promoter mutations with genotype and progression of liver disease

作　　者：刘悦晖[1] 丁静娟[1] 张权[1] 

机构地区：[1]贵阳医学院附属医院感染科实验室,贵阳550004

出　　处：《中华消化杂志》2005年第9期526-529,共4页Chinese Journal of Digestion

基　　金：国家自然科学基金资助项目(30360098)

摘　　要：目的探讨乙型肝炎病毒(HBV)前C区和基本核心启动子(BCP)区变异与基因型及疾病进展间的关系。方法收集HBV携带者(ASC)、慢性乙型肝炎(CHB)、肝炎肝硬化(LC)、肝细胞肝癌(HCC)患者血清148份,用半巢式聚合酶链反应扩增HBV前C/C基因部分片段,产物纯化后直接测序,检测前C区A1896及BCP区T1762/A1764变异。用S基因聚合酶链反应-限制性片段长度多态性分析(PCR-RFLP)方法确定HBV基因型。结果有128份血清能够成功分型和测序,其中B基因型60份,C基因型68份。在B基因型感染者中前C区A1896变异检出率(48.33%)明显高于C基因型感染者(29.41%,χ2=4.83,P<0.05);而BCP区T1762/A1764变异检出率却明显低于C基因型感染者,差异亦有统计学意义(30.00%∶73.54%,χ2=24.25,P<0.05)。前C区A1896变异在CHB、LC、HCC中的阳性检出率分别为46.88%(15/32)、39.39%(13/33)、51.52%(17/33),与ASC的13.33%(4/30)相比,P分别<0.05,差异有统计学意义。BCP区T1762/A1764变异检出率在HCC、LC组分别为87.88%(29/33)和72.73%(24/33),明显高于CHB组的37.50%(12/32)及ASC组10.00%(3/30)(P<0.05)。结论前C区A1896变异常见于B基因型感染者,而BCP区T1762/A1764变异C基因型感染者多见。除ASC外,前C区A1896变异与疾病进展关系不大,而BCP区T1762/A1764变异与乙型肝炎进展及预后相关。Objective To study association of hepatitis B virus（HHV） precore （pre c）/basic core promoter（BCP） mutations with the genotype or the progression of liver disease. Methods The serum samples from 148 patients with HBV relative diseases were collected, including ,31 asymptomatic carriers, 32 with chronic hepatitis B （CHB）, 40 with liver cirrhosis（LC） and 45 with hepatocellular carcinoma（HCC）. The genes covering HBV pre c and HCP were amplified by nested polymerase chain reaction （nPCR）. The PCR products were suhjected to direct sequencing and the mutations in pre c 1896 and BCP 1762/1764 were determined by sequence analysis. HBV genotypes were also detected in the sera by restriction fragment length polymorphism based on S-gene PCR products. Results Of 148 serum samples of HBV, 128 were successfully genotyped and sequenced. There were 60 genotype B and 68 genotype C. The mutation in pre c （A1896） was significantly higher in genotype B than in genotype C （48. 3% vs 29.34%, P〈（0.05）. On the contrary, the mutation at BCP （T1762/A1764） was significantly lower in genotype B than in genotype C （30. 0% vs 73. 5%, P〈0. 01）. The detection rate of pre c mutation （A1896） was almost same among CHB,LC and HCC. However, there was significant difference in the detection rate of BCP mutation （T1762/A1764） among patients with HCC, LC and CHB. Conclusions The mutations in the BCP region at nucleotide 1762/1764, which is common in genotype C, are closely related to progression of chronic liver disease. Mutation in the pre c （ 1 8 9 6 ） , which is frequent in genotype B, may contribute to inactivation of chronic liver disease.

关 键 词：乙型肝炎病毒 基本核心启动子 前C基因 基因型 

分 类 号：R512.62[医药卫生—内科学] R512.91[医药卫生—临床医学]