Shanxi Medical University, Department of Epidemiology, Taiyuan, Shanxi, China.
Shanxi Medical University, Center of Clinical Epidemiology and Evidence Based Medicine, Taiyuan, Shanxi, China.
Rev Inst Med Trop Sao Paulo. 2023 Sep 8;65:e46. doi: 10.1590/S1678-9946202365046. eCollection 2023.
PreS/S gene mutations could impact virus secretion, infection and immune evasion. However, the relationship between PreS/S mutations and intrauterine transmission has not yet been clarified. Thus, we aimed to explore the associations between PreS/S gene mutations of HBV isolated from mothers and intrauterine transmission. We analyzed the mutations of PreS/S regions of the HBV genome in mothers with HBV DNA levels ≥ 106 IU/mL whose neonates experienced HBV intrauterine transmission (transmission group, GT) and those whose neonates did not experience intrauterine transmission (control group, GC) analyzed using clone-based sequencing. In total, 206 sequences were successfully amplified, including 98 sequences (from 21 mothers) from GT and 108 sequences (from 20 mothers) from GC of genotype C for mutational analysis. Among the 1203 nucleotides of PreS/S regions, there were 219 (18.20%) base substitutions, of which 103 (47.03%) base mutations caused amino acid changes. F80S, A90V and I68T were mutation hotspots. Mothers in GT had a higher mutation rate of A90V in the PreS1 gene than mothers in GC. The A90V mutation increased the risk of HBV intrauterine transmission after adjusting the maternal age and the mode of delivery (OR = 6.23, 95% CI: 1.18-32.97). Moreover, the area under the ROC curve (AUC) for intrauterine transmission due to A90V and a combination of A90V with the mode of delivery were 0.723 (95% CI: 0.575 to 0.891, P = 0.011) and 0.848 (95% CI: 0.723 to 0.972, P < 0.001), respectively. Mothers with the A90V mutation in the PreS1 gene may be a potential risk factor for HBV intrauterine transmission.
前 S/S 区基因突变可能影响病毒的分泌、感染和免疫逃逸。然而，前 S/S 区突变与宫内传播之间的关系尚未阐明。因此，我们旨在探讨乙型肝炎病毒（HBV）前 S/S 基因突变与宫内传播的关系。我们分析了乙型肝炎病毒 DNA 水平≥106IU/mL 的 HBV 感染母亲的 HBV 前 S/S 区基因突变为 1203 个核苷酸，包括 98 个序列（来自 21 位母亲）来自 GT 和 108 个序列（来自 20 位母亲）来自 GC 的基因型 C 用于突变分析。在 PreS/S 区的 219 个（18.20%）碱基替换中，有 103 个（47.03%）碱基突变导致氨基酸改变。F80S、A90V 和 I68T 是突变热点。GT 组 PreS1 基因中的 A90V 突变率高于 GC 组母亲。调整母亲年龄和分娩方式后，A90V 突变增加了乙型肝炎病毒宫内传播的风险（OR=6.23，95%CI：1.18-32.97）。此外，A90V 及 A90V 与分娩方式联合导致宫内传播的 ROC 曲线下面积（AUC）分别为 0.723（95%CI：0.575-0.891，P=0.011）和 0.848（95%CI：0.723-0.972，P<0.001）。前 S1 基因中存在 A90V 突变的母亲可能是乙型肝炎病毒宫内传播的潜在危险因素。
