重型肝炎病人的乙肝病毒前C基因变异研究

对１１例重型肝炎病人乙型肝炎病毒（ＨＢＶ）ＤＮＡ直接序列进行分析以阐述变异特点。一次或套式ＰＣＲ扩增到的ＨＢＶＤＮＡ，以不对称ＰＣＲ法制备成单链模板后直接作序列分析。结果１１个病例中，９例有１～２个氨基酸替代变异：Ｇ１８９６→Ａ的替代，产生一个终止密码，见于１例抗－ＨＢｅ阳性的病人，第１７位（ＡＡ１７）缬氨酸被苯丙氨酸替代，见于１例ＨＢｅＡｇ阴性的病人，ＡＡ１５和ＡＡ２９的丝氨酸替代变异见于２例ＨＢｅＡｇ阴性、ＨＢＶ含量甚低的病例，１８５８Ｃ→Ｔ替代见于４例病人，与ＨＢｅＡｇ表型无关，无一伴有终２８变异，呈相互排斥现象。说明重型肝炎病人的ＨＢＶ前Ｃ基因存在多种变异类型。这些变异点只见于１～２例病人，似乎不是引发重型肝炎的重要原因，Ｇ１８９６→Ａ替代变异和ＡＡ１７的苯丙氨酸替代与ＨＢｅＡｇ阴性表型相关

HEPATITIS B VIRUS PRECORE GENE MUTATIONS IN FULMINANT HEPATITIS

Hepatitis B virus (HBV) precore gene mutations were studied in 11 patients with fulminant hepatitis by direct sequencing. HBV DNA was amplified by single or half nested PCR. Sequence analysis was performed by direct sequencing of single strand DNA from asymmetrical PCR. There were at least 1 2 amino acid substitutions in 9 of 11 patients. G to A mutation in nucleiotide (nt) 1896 which generate a stop codon in amino acid 28 was found in a anti HBeAg negative patients. Both AA15 and AA29 Serine substitutions were detected in 2 HBeAg negative and HBV low titer patients. T to C mutation in nt1858 was found in 4 patients, none of them had nt1896 stop mutation. There were many types of mutations in HBV precore region in patients with fulminant hepatitis, most of these mutations were seen in part of the patients, suggesting they were not crucial in the process of fulminant hepatitis. nt1896 stop mutation and AA17 Phe substtutions were related to HBeAg negatve phenotype.