不良结局聚集性乙型肝炎病毒感染家系基本核心启动子／前C区热点突变分析  

Analysis of hot mutations of basic core promoter and PreC region in familial clustering of hepatitis B virus infection with unfavorable prognoses

作　　者：杨瑗[1] 金李[1] 杜丹[1] 何英利[1] 刘锦锋[1] 王静[1] 王科[1] 马晓华[1] 李倩[1] 闫志[1] 弋锐田[1] 陈天艳[1] 赵英仁[1] 

机构地区：[1]西安交通大学医学院第一附属医院感染科,710061

出　　处：《中华传染病杂志》2015年第11期672-677,共6页Chinese Journal of Infectious Diseases

基　　金：国家科技重大专项（2008ZX10002-006,2012ZX10002007）;陕西省科学技术研究发展计划项目（2014N11-03-03-09）

摘　　要：目的了解HBV基本核心启动子（BCP）区及前C（PreC）区突变在不良结局家族聚集性HBV感染家系中不同疾病进展阶段的分布特点。方法共纳入39个不良结局家族聚集性HBV感染家系，利用PCR及直接测序法对慢性HBV携带者53例，CHB患者56例，肝硬化患者43例和肝细胞癌（HCC）患者28例进行基因分型及BCP／PreC序列分析。统计学处理采用独立样本t检验、χ2检验或Fisher确切概率法。结果在HCC患者中，A1762T／G1764A、C1766T、T1768A、A1846T、G1899A突变发生率分别为64．29％、25．00％、25．00％、28．57％和17．86％，显著高于慢性HBV携带者的37．74％、1．89％、0、7．55％和3．77％，差异有统计学意义（χ2值分别为5．186、8．885、14．503、4．859、4．603，均P〈0．05）；其中C1766T、T1768A突变在HCC患者中的发生率显著高于CHB患者的8．93％和5．36％，差异有统计学意义（χ2值分别为3．938、6．868，均P〈0．05）。A1762T／G1764A在C基因型中的突变发生率（59．12％）显著高于B基因型（16．13％），差异有统计学意义（χ2=13．118，P〈0．05）；A1752V、C1799G突变发生率在B基因型分别为90．32％和96。77％，显著高于C基因型的4、38％和1．46％，差异有统计学意义（7。值分别为110．409、142．825，均P〈0．05）。Logistic回归分析显示，与慢性HBV携带者比较，高龄、男性、ALT、AsT、HBVDNA〉1×10^4IU／mL、A1762T／G1764A、G1896A、C1766T、T1768A、G1899A、A1846T突变与HCC独立相关。与非HCC比较，高龄、男性、ALT、AST、G1896A、C1766T、T1768A、A1846T突变与HCC独立相关。结论A1762T／G1764A、C1766T、T1768A、A1846T、G1899A突变与不良结局家族聚集性HBV感染家系的疾病进展相关，主要与HCC进展相关；A1762T／G1764A、A1752V、C1799G突变在C基因到与B慕因型中存在苹异。Objective To investigate the distribution of hot mutations of basic core promoter （BCP） and PreC region in different stages of familial clustering of hepatitis B virus （HBV） infection with unfavorable prognoses. Methods Thirty-nine families with clustering of infection with unfavorable prognoses were enrolled in this study. All samples including 53 chronic HBV carriers, 56 chronic hepatitis B （CHB） patients, 43 liver cirrhosis （LC） patients and 28 hepatocellular carcinoma （HCC） patients were analyzed for genotypes and BCP/PreC mutations with polymerase chain reaction （PCR） and direct sequencing. Independent-samples t test was used for continuous variables, while χ2 test or Fisher exact probability test was used for dichotomous variables. Results Proportions of A1762T/G1764A, C1766T, T1768A, A1846T and G1899A in HCC patients were 64.29%, 25.00%, 25.00%, 28.57% and 17.86%,respectively, which were significantly higher than those in chronic HBV carriers （37.74 %, 1.89%, 0, 7.55 and 3.77%, respectively; χ2= 5. 186, 8. 885, 14. 503, 4. 859 and 4. 603, respectively, all P〈0.05）. C1766T and T1768A were significantly associated with HCC compared with CHB which were 8. 93% and 5.36%, respectively （χ2 =3. 938 and 6. 868, respectively; both P〈0.05）. Mutation of A1762T/G1764A ingenotypeC （59.12%） was higher than genotype B （16. 13% χ2=13.118, P〈0.05）. Mutations of A1752V and C1799G in genotype B were 90.32% and 96.77%, respectively, which were higher than that in genotype C （4. 38% and 1. 46%, respectively; χ2 = 110. 409 and 142. 825, respectively; both P〈 0.05）. Logistic regression analysis showed that old age, male gender, abnormal alanine aminotransferase （ALT）, abnormal aspartate transaminase （AST）, HBV DNA〉 1 × 10^4 IU/mL, A1762T/G1764A, G1896A, C1766T, T1768A, G1899A and A1846T were independently associated with HCC compared with chronic HBV carriers. Old age, male gender, abnormal ALT, abnormal AST, G1896A, C1766T, T1768A and A1846T were independently

关 键 词：肝炎 乙型 家族聚集 不良结局 病毒突变 

分 类 号：R512.62[医药卫生—内科学]