乙型肝炎病毒不同位点变异及其分布与肝功能酶活力的表达关系

Relationship Between Variation and Distribution of Differential Gene Sites of Hepatitis B Virus and Enzymatic Activity of Liver Function

目的探讨乙型肝炎病毒(HBV)YMDD、G1896A和A1762T变异及其分布与肝功能酶活力表达关系。方法应用核酸阵列和核酸杂交技术对277例经抗病毒治疗>2年慢性乙型肝炎患者的血清分别检测YMDD、G1896A和A1762T变异,采用TaqMan荧光探针技术和速率法进一步分别检测各变异标本的HBV DNA含量和肝功能酶活力(ALT、AST、-γGT)。结果YMDD、G1896A和A1762T变异在HBeAg(+)模式和HBeAg(-)模式组分别为46.2%和18.7%、3.5%和22.8%、16.71%和17.9%,HBV DNA含量>105拷贝/ml分别占79.5%、18.8%、61.9%;G1896A或A1762T变异时,3种酶活力显著高于YMDD变异组(P<0.01),G1896A和A1762T比较差异无统计学意义(P>0.05),YMDD变异组与无变异的HBeAg(+)模式组比较,ALT和AST活力显著上升(P<0.01),而γ-GT差异无统计学意义(P>0.05)。结论G1896A变异以HBeAg(-)表达和HBV低水平复制为主,A1762T变异与HBeAg表达无明显相关性,HBV多数以高水平复制,YMDD变异以HBeAg(+)和HBV高水平复制为主,YMDD变异引发急性肝细胞轻微损伤,G1896A或A1762T变异与损伤肝细胞整个进程有关。

OBJECTIVE To study the relationship between mutation and distribution of YMDD, G1896A and A1762T and enzymatic activity of liver function. METHODS The mutation of YMDD, G1896A and A1762T was detected by nucleic acid uniarray and hybridization technique in sera of 277 cases treated by anti-HBV over 2 years respectively. Contents of HBV DNA and enzymatic activity were determined by PCR-fluorescence quantity and speed in the sera with gene mutation respectively. RESULTS The variant rate of YMDD, G1896A and A1762T was 46.2% and 18.7%, 3, 5% and 22.8%, and 16.71% and 17.9M, respectively, and their contents of HBV DNA higher than 105 copies/ml, were 79.5%, 18.8% and 61.9%, respectively. Their enzymatic activity in the groups with G1896A or A1762T variation was significantly higher than that in the group with YMDD variation （P〈0.01）, but without significant difference （P〉0.05） between G1896A and A1762T variation groups. The activity of ALT or AST was significantly higher in YMDD variation group compared with that in HBeAg （＋） group without variation, but the γ-GT hadn＇t statistical difference （P〉0.05）. CONCLUSIONS G1896A Variation principally distributes in HBeAg （-） group that expressed low level HBV DNA. A1762T Variation and HBeAg （＋） havenPt obvious correlation. YMDD variation principally distributes in HBeAg （＋） group that expressed high lever HBV DNA. YMDD variation initiates acute damage of liver cell. The variation of G1896A or A1762T may contribute to progressive damage of chronic liver disease.