重型乙型肝炎病人中乙型肝炎病毒C基因启动子变异的研究

Hepatitis B virus core promoter mutations in patients with fulminant hepatitis

目的 了解重型乙型肝炎（ 乙肝） 病人血清乙肝病毒（ＨＢＶ）ＤＮＡＣ基因启动子（ＣＰ） 的变异。方法 对用聚合酶链反应（ＰＣＲ） 法扩增的血清ＨＢＶＤＮＡ 直接测序。结果 ７ 例亚急性重型肝炎病人的ＨＢＶ 分离株ＣＰ区分别有２～１２ 个替代变异，１ 例病人有１１ｂｐ 的碱基插入。ＣＰ变异主要发生于ＣＰ的第１ 和第２ 个ＡＴ丰富区，ｎｔ１ ７６２ 和ｎｔ１ ７６４ 的替代变异见于７ 例亚急性重型肝炎病人的４ 例中，是ＣＰ变异的热点，其中３ 例ＨＢｅＡｇ 阴性，说明和ＨＢｅＡｇ 阴性表型相关。ＣＰ的第３ 个ＡＴ丰富区、ＨＢＶ逆转录起始位点（ＤＲ１） 和前Ｃ基因、前基因组转录起始位点未见变异。结论 重型肝炎病人的ＨＢＶＣＰ区存在较多的变异，ＣＰ变异主要发生于和前Ｃ基因相关的第１ 和第２ 个ＡＴ丰富区，可能和ＨＢｅＡｇ

Objective To detect hepatitis B virus core promoter (CP) mutations in patients with fulminant hepatitis.Methods Polymerase chain reaction amplified serum HBV DNA fragments were directly sequenced. Results There were 2 12 nucleotide substitutions in CP region in the 7 subacute fulminant hepatitis patients studied. An 11 bp nucleotides insertion was found in one patient. Mutations in CP were usually seen in the first and the second A T rich regions. The A to T mutation at nt 1 762 and G to A mutation at nt 1 764 were found in 4 cases, 3 of them were HBeAg negative. The third A T rich region was kept intact in all the 7 patients, so did the initial site of HBV replication (DR1) and the intial site of mRNA transcription (1 783/1784 or 1 790±1 for precore mRNA and 1818 for pregenome C/P mRNA).Conclusion CP mutations in patients with fulminant hepatitis are common, most of the CP variations occur in the first and the second A T rich regions, and these mutations may impede the transcription of precore mRNA and affect the expression of HBeAg.