HBe抗体阳性的肝炎静息与活动者HBV X及C基因变异的对比研究  

X gene and precore／core region mutations in hepatitis B virus genome in subjects positive for anti-HBe a comparative study of asymptomatic carriers and patients with chronic active hepatitis

作　　者：彭劼[1] 骆抗先[1] 侯金林[1] 章廉[1] 郭亚兵[1] 阎丽[1] 

机构地区：[1]第一军医大学南方医院感染内科,广东广州510515

出　　处：《第一军医大学学报》2001年第9期665-668,共4页Journal of First Military Medical University

基　　金：国家自然科学重点课题基金(39630280)

摘　　要：目的 研究乙型肝炎病毒（HBV）X及C基因变异是否与e抗体阳性的HBV感染的不同临床现象相关。方法 对e抗体阳性14例无症状携带（AsC）者及e抗体阳性14例慢性活动性肝炎（CAH）患者的血清HBV X及前C/C基因序列进行克隆、测序。结果 AsC组中，12例（85.7%）X基因上出现核苷酸插入、缺失、点突变，导致X基因编码的框移而提前终止，或提前出现终止密码子，从而使X蛋白被截短，而14例CAH均编码154个氨基酸的完整X蛋白，没有出现上述X基因的变异；AsC与CAH组中，前C终28变异分别为7例和10例；CAH组C区平均发生氨基酸替代数量（5.71±2.20）显著高于AsC组（2.71±1.73，P<0.001）；C区Val60、Gly87、Leu97变异仅出现于CAH组而不见于AsC病例中，Gln79、Gln135变异多见于CAH而罕见于AsC病例中。结论 X基因的变异所致X蛋白的截短与e抗体阳性肝炎静息的无症状携带临床现象密切相关；C基因的热点变异与e抗体阳性的HBV感染肝炎活动的临床现象密切相关。 Objective To investigate whether the mutations in X and precore/core region of hepatitis B virus (HBV) genome are responsible for different clinical profiles in cases positive for the antibody against hepatitis B e antigen. Methods The nucleotide sequences of X and precore/core genes of serum HBV were cloned and sequenced in 14 asymptomatic carriers (AsCs) and 14 chronic active hepatitis (CAH) patients with antibody against hepatitis B e antigen. Results Twelve of 14 AsCs (85.7%) had insertions, deletions or point mutations in the nucleotide sequence of X region resulting in truncation of the X protein by creating frame shift mutation or a new stop codon, whereas no patient with CAH had those X gene mutations. The precore stop codon mutation was found in 7 AsCs and 10 CAH cases. The number of amino acid changes in the core region of HBV in CAH group （5.71±2.20） was significantly greater than that in the AsC group (2.71±1.73，P<0.001). We detected hot spots for core mutation, which showed characteristic localizations and specific substitutions, with Val60, Gly87 and Leu97 exclusively in CAH patients, and Gln79 and Gln135 mostly in CAH group. Conclusion In anti-HBe-positive HBV carriers, mutations resulting in the truncation of the X protein were closely associated with the clinical asymptomatic profiles and the subsequent quiescence in hepatitis activity, and the hot spot mutations of HBV core gene were closely associated with the clinical severity of chronic hepatitis B.

关 键 词：乙型肝炎病毒 X基因变异 C基因变异 无症状携带 慢性活动性肝炎 

分 类 号：R512.62[医药卫生—内科学]