Akahane Y, Yamanaka T, Suzuki H, Sugai Y, Tsuda F, Yotsumoto S, Omi S, Okamoto H, Miyakawa Y, Mayumi M
First Department of Internal Medicine, Yamanashi Medical College, Japan.
Gastroenterology. 1990 Oct;99(4):1113-9. doi: 10.1016/0016-5085(90)90632-b.
Some patients with type B chronic active hepatitis have a high titer of hepatitis B virus DNA despite antibody against e antigen in the serum. Clones of hepatitis B virus were propagated from the sera of seven patients with this disease, and the precore region was sequenced. Essentially all clones (128/131 or 98%) showed a point mutation from guanine to adenine at nucleotide 83, converting codon 28 for tryptophan (TGG) to a stop codon (TAG); the second guanine-to-adenine point mutation at nucleotide 86 was identified in only 29 clones from two patients. In patients followed up since they had hepatitis B e antigen, a shift from guanine to adenine was observed at nucleotide 83 along with the seroconversion to the antibody to e antigen. The precore-region product is required for the synthesis and secretion of e antigen from hepatocytes. A point mutation from guanine to adenine at nucleotide 83 observed in the seven patients, therefore, would be responsible for disturbed secretion of e antigen.
一些B型慢性活动性肝炎患者血清中虽有e抗原抗体，但乙肝病毒DNA滴度仍很高。从7例该病患者的血清中培养出乙肝病毒克隆，并对前核心区进行测序。基本上所有克隆（128/131或98%）在核苷酸83处都有一个从鸟嘌呤到腺嘌呤的点突变，将色氨酸密码子28（TGG）转变为终止密码子（TAG）；仅在两名患者的29个克隆中发现了核苷酸86处的第二个从鸟嘌呤到腺嘌呤的点突变。自出现乙肝e抗原以来接受随访的患者中，在核苷酸83处观察到从鸟嘌呤到腺嘌呤的转变，同时血清转化为e抗原抗体。前核心区产物是肝细胞合成和分泌e抗原所必需的。因此，在这7例患者中观察到的核苷酸83处从鸟嘌呤到腺嘌呤的点突变，可能是导致e抗原分泌紊乱的原因。
