Ballard A L, Boxall E H
Public Health Laboratory, Heartlands Hospital, Birmingham, United Kingdom.
J Med Virol. 2000 Dec;62(4):463-70. doi: 10.1002/1096-9071(200012)62:4<463::aid-jmv11>3.0.co;2-0.
A point mutation assay was used to study the codon 28 and codon 1 precore mutant status of 310 chronic hepatitis B carriers (82 HBeAg positive and 228 HBeAg negative). Fourteen of 228 (6%) of HBeAg negative carriers had high levels of serum HBV DNA. Nine of these were explained by precore variants, three by core promoter variants, and two were not explained by recognised precore changes. Nested PCR detected serum HBV DNA in 36% (82/228) of HBeAg negative carriers and 63% (52/82) of these had precore variants. Four of 82 (4%) of the HBeAg positive carriers had precore variants, all as mixed mutant/wild type populations and evidence indicated that these carriers were seroconverting. Overall 23% (52/228) of HBeAg negative carriers had both serum HBV DNA and codon 1 or 28 precore mutations. A sexual transmission event from an HBeAg negative carrier with a relatively low serum HBV DNA level (10(4)-10(6) genome copies/ml) and only core promoter mutations was observed. Despite high rates of variant carriage in the antenatal sub-group perinatal transmission was not observed. The results of direct sequencing on 45 carriers validated the point mutation assay and also showed that codon 28 mutations were only seen in carriers with the genotype CCT at codon 15. For the Caucasian population a higher prevalence of codon 28 mutations (13/25 or 52%) than expected was seen. Liver biopsy data indicated that there was no link between the presence or absence of precore mutants and the severity of liver disease.
采用点突变分析方法研究了310例慢性乙型肝炎携带者（82例HBeAg阳性和228例HBeAg阴性）的28密码子和1密码子前核心区突变状态。228例HBeAg阴性携带者中有14例（6%）血清HBV DNA水平较高。其中9例由前核心区变异解释，3例由核心启动子变异解释，2例无法用已知的前核心区变化解释。巢式PCR在36%（82/228）的HBeAg阴性携带者中检测到血清HBV DNA，其中63%（52/82）有前核心区变异。82例HBeAg阳性携带者中有4例（4%）有前核心区变异，均为混合突变/野生型群体，有证据表明这些携带者正在发生血清学转换。总体而言，23%（52/228）的HBeAg阴性携带者同时有血清HBV DNA和1密码子或28密码子前核心区突变。观察到1例HBeAg阴性携带者（血清HBV DNA水平相对较低，为10⁴ - 10⁶基因组拷贝/ml，仅有核心启动子突变）发生了性传播事件。尽管产前亚组中变异携带率较高，但未观察到围产期传播。对45例携带者进行直接测序的结果验证了点突变分析方法，还显示28密码子突变仅见于15密码子基因型为CCT的携带者。对于白种人群体，观察到28密码子突变的患病率（13/25或52%）高于预期。肝活检数据表明，前核心区突变的有无与肝病严重程度之间没有关联。
