乙型肝炎病毒感染者C基因突变株的检测及意义

Detection of Mutation of Viral C Gene in Cases With Hepatitis B Virus Infection and its Significance

目的 :了解乙型肝炎病毒 (HBV)感染者前C/C区基因变异热点的突变情况及其意义。方法 :采用巢式PCR方法和限制性片段长度多态性 (RFLP)技术检测 117例HBV感染者血清HBV前C区终 2 8和C区L97突变株。结果 :急性乙型肝炎、慢性HBV携带者、慢性乙型肝炎、活动性肝硬化、原发性肝癌、重型乙型肝炎患者终 2 8检出率分别为 15 .3% (2 / 13)、9 1% (1/ 11)、2 5 0 % (9/ 36 )、75 0 % (12 / 16 )、5 0 0 % (5 / 10 )、4 8.3% (15 / 31) ;L97突变株检出率分别为 2 3 1% (3/ 13)、2 7.3% (3/ 11)、5 0 0 % (18/ 36 )、6 8.8% (11/ 16 )、70 0 % (7/ 10 )、71 0 % (2 2 / 31)。HBV感染者终2 8和L97突变株并存 32例。L97点突变和终 2 8点突变之间存在关联性 (χ2 =9.2 5 ,P <0 .0 1)。结论 :急性乙型肝炎和无症状HBV携带者突变株检出率明显低于活动性肝硬化、原发性肝癌、重型肝炎。C基因的热点变异与病情的严重性相关。

Objective: Our aim was to investigate states of hepatitis B virus (HBV) C gene mutations and its significance. Methods: Serum samples from 117 cases with HBV infection were screened for nt 1896 G→A introducing a stop coden (TAG) and nt 2189 A→C substituting isoleucine (ATC) for leucin (CTC) with nested polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) analysis. Results: A few mutation points at nt 1896 and nt 2189 were found in actue hepatitis B and chronic asymptomatic virus carrier. Mutant rate at nt 1896 was 75% (12 of 16),50% (5 of 10),48.3% (15 of 31), and 25%(9 of 36) in acute liver cirrhosis, hepatocellular carcinoma, severe exacerbation and fulminant hepatitis, chronic hepatitis respectively. Mutant rate at nt 2189 was 68.8%(11 of 16),70%(7 of 10),71%(22 of 31), and 50%(18 of 36) in correspondence with clinical type of mutation at nt 1896.There were point mutations of both nt 1896 and nt 2189 in 32 cases. Correlation existed between point variants (χ 2=9.25, P<0.01). Conclusion: Both point mutations were different in cases with variant clinical types of hepatitis B and were related to the disease activity. The HBV with a mutation in the hypervariable region of the core region have more frequency introducting stop codon at nt 1896.