Hasegawa K, Huang J K, Wands J R, Obata H, Liang T J
Department of Medicine, Harvard Medical School, Massachusetts General Hospital Cancer Center, Charlestown 02129.
Virology. 1991 Nov;185(1):460-3. doi: 10.1016/0042-6822(91)90799-h.
We studied the precore DNA sequences of hepatitis B viral genomes in five patients with fulminant hepatitis B and in five with acute self-limited hepatitis B from Japan. Using the polymerase chain reaction, three to four independent HBV DNA clones from each patient were obtained and analyzed. We demonstrated that patients with fulminant hepatitis B carried HBV genomes with a G to A mutation at nucleotide positions 1898 (five of five patients; 18 of 18 clones, 100%) and 1901 (five of five patients; 12 of 18 clones, 66%) in the precore region. The first mutation results in an in-phase stop codon (TAG) in the precore open reading frame and the absence of HBeAg production. In contrast, a G to A mutation was found in 6 of 16 clones (37%) in position 1898 and in 0 of 16 clones (0%) in position 1901 from patients with acute self-limited hepatitis. We concluded that both of the precore mutations are commonly associated with fulminant hepatitis B and may contribute to the pathogenesis of fulminant hepatitis. A hypothetical model for the biological significance of these two mutations is proposed.
我们研究了来自日本的5例暴发性乙型肝炎患者和5例急性自限性乙型肝炎患者的乙型肝炎病毒基因组前核心DNA序列。通过聚合酶链反应，从每位患者获得三到四个独立的HBV DNA克隆并进行分析。我们发现，暴发性乙型肝炎患者在前核心区域的核苷酸位置1898（5例患者均为；18个克隆中的18个，100%）和1901（5例患者均为；18个克隆中的12个，66%）存在G到A的突变。第一个突变导致前核心开放阅读框中出现同相位终止密码子（TAG），且不产生HBeAg。相比之下，急性自限性乙型肝炎患者的16个克隆中有6个（37%）在位置1898处发现G到A的突变，而在位置1901处的16个克隆中未发现（0%）。我们得出结论，这两种前核心突变均与暴发性乙型肝炎常见相关，可能对暴发性肝炎的发病机制有影响。提出了这两种突变生物学意义的假设模型。
