乙型肝炎病毒表面抗原和表面抗体共阳性感染者病毒基因PreC/C区变异特征
Characteristics of PreC/C region mutations in chronic HBV-infected patients with coexistence of hepatitis B surface antigen and antibody
摘要目的:探讨HBsAg和抗-HBs共阳性慢性HBV感染者病毒基因组PreC/C区变异特征。方法:选取湖州市中心医院2020年11月至2021年12月收集的32例HBsAg和抗-HBs共阳性慢性HBV感染者为共阳性组,选取同期的32例HBsAg阳性而抗-HBs阴性的慢性HBV感染者为单阳性组,对血清中病毒基因组PreC/C区进行PCR扩增并测序,比较两组间PreC/C区基因核苷酸突变和氨基酸替换特征差异。结果:共阳性组共成功测序27例,单阳性组成功测序31例。共阳性组在C区2080、2189、2242三个位点的核苷酸突变率均高于单阳性组,差异有统计学意义( χ2=5.48、8.36和4.15, P值分别为0.019、0.004和0.042);在C区第97氨基酸位点突变率(51.85%,14/27)高于单阳性组(16.13%,5/31),差异有统计学意义( χ2=8.22, P=0.004)。共阳性组中C区B细胞表位(AA105-116)中的氨基酸突变率(40.74%,11/27)和突变频率(每100个氨基酸发生突变个数为7.10)显著高于单阳性组的氨基酸突变率(16.13%,5/31)和突变频率(每100个氨基酸发生突变个数为3.23),差异均有统计学意义( χ2=5.43和4.30, P值分别为0.020和0.038)。 结论:共阳性者PreC/C区一些位点突变高于单阳性者,PreC/C区部分功能区域突变可能与共阳性者的病毒低水平慢性持续感染有关。
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abstractsObjective:To investigate the characteristics of PreC/C gene mutations in patients with coexistence of HBsAg and anti-HBs.Methods:A total of 32 chronic HBV-infected patients with both HBsAg and anti-HBs positive in Huzhou Central Hospital from November 2020 to December 2021 were selected as the co-positive group, and 32 chronic HBV-infected patients with HBsAg positive and anti-HBs negative during the same period were selected as the single positive group. Nucleic acid was extracted from serum samples. The PreC/C region of the HBV genome was amplified using PCR and subsequently sequenced, allowing for a comparative analysis of the nucleotide mutation and amino acid substitution of the PreC/C region between the two groups.Results:There were 27 cases and 31 cases successfully sequenced in co-positive group and single positive group, respectively. The mutation rates of nucleic acid at the 2080, 2189 and 2242 sites in the C region of the co-positive group were significantly higher than those of the single positive group ( χ2=5.48, 8.36 and 4.15, P=0.019, 0.004 and 0.042). At the amino acid level, the mutation rate at C-97 amino acid site in co-positive group (51.85%, 14/27) was significantly higher than that in single positive group (16.13%, 5/31) ( χ2=8.22, P=0.004). Mutation rate (40.74%, 11/27) and frequency (the number of mutations per 100 amino acids was 7.10) of the amino acid in B cell epitope (AA105-116) of C region in co-positive group were significantly higher than those in single positive group (16.13%, 5/31; the number of mutations per 100 amino acids was 3.23) ( χ2=5.43 and 4.30, P=0.020 and 0.038). Conclusions:The mutations at certain sites in PreC/C region in co-positive group are significantly higher than those in single-positive group. Mutations in specific functional regions of the PreC/C region may be related to the low-level persistent HBV infection in co-positive individuals.
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