【摘要】 [目的]探讨乙型肝炎病毒X区基因(Hepatitis B virus X gene, HBVx)突变情况与慢性乙型肝炎病毒(hepatitis B virus, HBV)感染患者血清中血管内皮生长因子-C(vascular endothelial growth factor-C,VEGF-C)及血管内皮生长因子-D(vascular endothelial growth factor-D,VEGF-D)表达的相关性。[方法]收集HBV-DNA定量≥10~3拷贝/ml的慢性乙型病毒性肝炎患者55例、肝硬化50例、肝细胞癌(hepatocellular carcinoma, HCC)50例。提取患者血清中HBV-DNA,采用巢氏PCR方法扩增HBVx基因，对产物进行基因测序，测序结果通过seqman软件与HBVx基因野生型对比分析突变位点。酶联免疫吸附测定法检测患者血清中VEGF-C及VEGF-D浓度。通过χ~2检验、单因素方差分析、秩和检验等方法对数据加以处理。[结果]肝病患者血清中HBVx常见的突变位点依次为：G1613 A、A1652 G、C1653T、T1753G、A1762T/G1764A、C1673 T、G1676 A,其中C1653T、A1762T/G1764A、T1753G位点在HCC组中突变率显著高于CHB组和肝硬化组。VEGF-C及VEGF-D血清浓度在HCC组中表达明显高于非HCC组。采用秩和检验对二者进行分析发现，具有C1653T、A1762T/G1764A或T1753G三个位点突变的HCC患者中VEGF-C的血清浓度明显高于CHB组和肝硬化组。[结论]HBVx中的C1653T、A1762T/G1764A和T1753G位点突变在HCC患者中显著升高，且与VEGF-C的血清浓度相关，提示这3个突变位点可能在HCC的发生发展中发挥作用。更多还原

【Abstract】 [Objective]To explore the relationship between Hepatitis B virus X gene(HBVx)mutation and the serum expression of vascular endothelial growth factor-C(VEGF-C)and vascular endothelial growth factor-D(VEGF-D)in the patients with chronic hepatits B virus(HBV)infection.[Methods]The serum samples of patients with HBV infection were collected including 55 chronic hepatitis B patients, 50 cirrhosis patients, and 50 HCC patients.The HBVx gene sequences were amplificated from the serum samples by polymerase chain reaction(PCR).The amplified products were subsequently sequenced, and compared with those reported in GenBank to find the variable sites.The level of VEGF-C and VEGF-D from serum samples were detected by enzyme-linked immunosorbent assay.[Results]The level of VEGF-C and VEGF-D were significantly higher in primary liver cancer group than other groups.The common HBVx gene mutation sites include: G1613 A,A1652 G,C1653T,T1753G,A1762T/G1764A,C1673 T and G1676 A.The C1653T,A1762 T/G1764 A,and T1753G mutation rates in the HCC group were significantly higher than the cirrhosis group(P<0.001).Furthermore, the serum concentrations of VEGF-C in HCC patients with three site mutations of C1653T,A1762 T/G1764 A or T1753G were significantly higher than the non-mutated group(P<0.001).[Conclusion]The C1653T,A1762T/G1764A and T1753G site mutations in HBVx are more frequent in HCC patients and associated with the expression of VEGF-C,implying that these mutations may be involved in the development and progression of hepatocellular carcinoma.更多还原