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目的:探讨乙型肝炎病毒X蛋白(hepatitis B virus X protein,HBx)氨基端1～90位氨基酸(amino acid,AA)变异与肝细胞癌发生之间的关系。方法:采用PCR扩增产物直接测序的方法,对48例肝癌组织、159例肝癌和144例慢性肝炎患者血清中HBVX基因进行序列分析。通过病例-对照研究HBx变异与肝癌发生之间的关系。结果:肝癌组织中HBx氨基端变异集中于1～49 AA区域,突变率为4.1%;50～90 AA为保守区,突变率仅为0.46%。血清检测结果显示,HBx氨基端突变在肝癌患者中的发生率显著高于肝炎患者(2.2%vs1.8%,P<0.05);HBx第36位Ala/Thr/Pro→Ser的突变,在肝癌患者中的发生率为10.1%,显著高于肝炎患者中的2.1%[P<0.01,比数比(odds ratio,OR)=5.259,95%可信区间为1.499～18.444)]。A/T/P36S突变仅发生于C基因型病毒。结论:HBx氨基端突变的累积可能与肝癌的发生有关。HBx A/T/P36S突变能增加C基因型HBV感染者发生肝癌的危险度。
Objective: To investigate the relationship between the amino terminal amino acid (amino acid, amino acid residues 1-90) of hepatitis B virus X protein (HBx) and the occurrence of hepatocellular carcinoma (HCC). Methods: HBV X gene was sequenced in 48 cases of HCC, 159 cases of HCC and 144 cases of chronic hepatitis B virus by direct sequencing of PCR products. A case-control study of the relationship between HBx mutation and the development of hepatocellular carcinoma. Results: The amino acid mutations of HBx in hepatocellular carcinoma were concentrated in the region of 1 to 49 AA, with a mutation rate of 4.1%. 50 to 90 AA was a conserved region with a mutation rate of 0.46%. The results of serum test showed that the mutation of amino acid sequence of HBx in HCC was significantly higher than that in hepatitis (2.2% vs1.8%, P <0.05). The mutation of Ala / Thr / Pro → Ser 36 in HBx The incidence in patients was 10.1%, significantly higher than 2.1% in patients with hepatitis [P <0.01, odds ratio (OR) = 5.259, 95% confidence interval, 1.499-18.444)]. The A / T / P36S mutation occurs only in the C genotype virus. Conclusion: The accumulation of amino terminal mutations in HBx may be related to the occurrence of hepatocellular carcinoma. HBx A / T / P36S mutations can increase the risk of HCC in patients with HBV genotype C infection.