Su Zhengqin, Su Yongjian, Shen Xiaozhen, Zhang Jiawei, Zeng Ting, Li Jialing, Chen Shiyi, Shao Kai, Zhang Shiyue, Luo Dan, Hu Liping, Guo Xiaojing, Li Hai
School of Public Health and Management, Guangxi University of Chinese Medicine, China; Key Laboratory of Integrated Traditional Chinese and Western Medicine for High-incidence Infectious Diseases, Guangxi, China.
Ruikang Hospital Affiliated to Guangxi University of Chinese Medicine, China.
Infect Genet Evol. 2025 Jan;127:105705. doi: 10.1016/j.meegid.2024.105705. Epub 2024 Dec 12.
The goal is to identify methylation sites linked to transmission and their impact on host gene expression and HBV spread, aiming to uncover new molecular targets for preventing and treating intrauterine HBV infection.
This study recruited 1205 infants born to HBsAg-positive mothers in Liuzhou City, China, between July 2023 and January 2024. Infants were followed up at 7-12 months of age and classified as HBsAg-positive (case, n = 5) or HBsAg-negative (control, n = 14) based on serological testing. Peripheral blood samples were collected for DNA extraction. DNA methylation profiling was performed using the Illumina Infinium MethylationEPIC BeadChip (850 K). Data were processed using the ChAMP package in R, including quality control, normalization, and identification of Differentially Methylated Positions (DMPs) and differentially methylated regions (DMRs). DMPs and DMRs were annotated using ANNOVAR 2018Apr16, and GO enrichment analysis was conducted using DAVID. The study was approved by the Guangxi University of Chinese Medicine Ethics Committee, and informed consent was obtained.
We identified 734,978 DMPs and 660 DMRs, with 1813 DMPs and 221 DMRs showing significant differences between groups. HBV-infected infants exhibited lower overall genomic methylation levels, with significant concentrations in gene body regions and CpG islands. GO enrichment analysis indicated that differentially methylated genes were enriched in processes related to cell adhesion and calcium ion binding.
Prenatal HBV exposure was associated with significant infant hypomethylation, particularly in regulatory regions like TSS1500, TSS200, and CpG islands, potentially impacting gene expression. Enrichment of immune-related pathways among differentially methylated genes suggests that HBV may alter infant immune development through epigenetic modifications.
目标是确定与传播相关的甲基化位点及其对宿主基因表达和乙肝病毒传播的影响，旨在发现预防和治疗宫内乙肝病毒感染的新分子靶点。
本研究招募了2023年7月至2024年1月期间在中国柳州市出生的1205名母亲为乙肝表面抗原阳性的婴儿。在婴儿7至12个月大时进行随访，并根据血清学检测将其分为乙肝表面抗原阳性（病例组，n = 5）或乙肝表面抗原阴性（对照组，n = 14）。采集外周血样本进行DNA提取。使用Illumina Infinium MethylationEPIC BeadChip（850K）进行DNA甲基化谱分析。使用R语言中的ChAMP软件包对数据进行处理，包括质量控制、标准化以及差异甲基化位点（DMP）和差异甲基化区域（DMR）的鉴定。使用ANNOVAR 2018Apr16对DMP和DMR进行注释，并使用DAVID进行基因本体（GO）富集分析。本研究经广西中医药大学伦理委员会批准，并获得了知情同意。
我们鉴定出734,978个DMP和660个DMR，其中1813个DMP和221个DMR在两组之间存在显著差异。乙肝病毒感染的婴儿总体基因组甲基化水平较低，在基因体区域和CpG岛中有显著集中。GO富集分析表明，差异甲基化基因富集于与细胞黏附和钙离子结合相关的过程。
产前乙肝病毒暴露与婴儿显著的低甲基化有关，特别是在转录起始位点1500（TSS1500）、转录起始位点200（TSS200）和CpG岛等调控区域，这可能会影响基因表达。差异甲基化基因中免疫相关途径的富集表明，乙肝病毒可能通过表观遗传修饰改变婴儿的免疫发育。
