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

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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 investigate the relationship between HBV genotypes and disease progression in hepatitis B virus (HBV) precore and basic core promoter (BCP) regions. Methods 148 serum samples collected from patients with chronic hepatitis B (CHB), cirrhosis (LC) and hepatocellular carcinoma (HCC) were collected. HBV pre-C / C was amplified by semi-nested polymerase chain reaction Gene fragments, the product was purified directly sequencing, detection of pre-C area A1896 and BCP area T1762 / A1764 variation. HBV genotypes were determined using the S gene polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Results A total of 128 serum samples were successfully genotyped and sequenced, including 60 genotypes of B and 68 genotypes of C genotypes. The positive rate of A1896 mutation in pre-C region (48.33%) was significantly higher in patients with genotype B than in those with genotype C (29.41%, χ2 = 4.83, P <0.05) But significantly lower than genotype C infection, the difference was also statistically significant (30.00%: 73.54%, χ2 = 24.25, P <0.05). The positive rates of A1896 mutation in pre-C region were 46.88% (15/32), 39.39% (13/33), 51.52% (17/33) in CHB, LC and HCC, respectively, / 30), P <0.05, the difference was statistically significant. The detection rate of mutation of T1762 / A1764 in BCP area was 87.88% (29/33) and 72.73% (24/33) in HCC group and LC group, respectively, which was significantly higher than 37.50% (12/32) in CHB group and 10.00% in ASC group (3/30) (P <0.05). Conclusion Pre-C region A1896 mutation is common in patients with genotype B infection, and BCP region T1762 / A1764 variant C genotype infection more common. In addition to ASC, A1896 mutation in pre-C region has little to do with disease progression, while T1762 / A1764 mutation in BCP region is associated with the progress and prognosis of hepatitis B.
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