B型肝炎病毒感染者精子中父亲印迹基因启动子区甲基化差异分析

Differential methylation patterns in paternally imprinted gene promoter regions in sperm from hepatitis B virus infected individuals  

B型肝炎病毒感染者精子中父亲印迹基因启动子区甲基化差异分析

Authors: Wu B, Sheng Y, Yu W, Ruan L, Geng H, Xu C, Wang C, Tang D, Lv M, Hua R, Li K.

Source：BMC Mol Cell Biol. 2024 Aug 1;25(1):19. doi: 10.1186/s12860-024-00515-7.

Abstract

Background: Hepatitis B virus (HBV) infection poses a substantial threat to human health, impacting not only infected individuals but also potentially exerting adverse effects on the health of their offspring. The underlying mechanisms driving this phenomenon remain elusive. This study aims to shed light on this issue by examining alterations in paternally imprinted genes within sperm.

Methods: A cohort of 35 individuals with normal semen analysis, comprising 17 hepatitis B surface antigen (HBsAg)-positive and 18 negative individuals, was recruited. Based on the previous research and the Online Mendelian Inheritance in Man database (OMIM, https://www.omim.org/ ), targeted promoter methylation sequencing was employed to investigate 28 paternally imprinted genes associated with various diseases.

Results: Bioinformatic analyses revealed 42 differentially methylated sites across 29 CpG islands within 19 genes and four differentially methylated CpG islands within four genes. At the gene level, an increase in methylation of DNMT1 and a decrease in methylation of CUL7, PRKAG2, and TP53 were observed. DNA methylation haplotype analysis identified 51 differentially methylated haplotypes within 36 CpG islands across 22 genes.

Conclusions: This is the first study to explore the effects of HBV infection on sperm DNA methylation and the potential underlying mechanisms of intergenerational influence of paternal HBV infection.

Keywords: Hepatitis B virus; Imprinted gene; Methylation; Paternally; Sperm.

摘要

背景资料：B型肝炎病毒（HBV）感染对人类健康构成重大威胁，不仅影响感染个体，而且可能对其后代的健康产生不利影响。驱动这一现象的根本机制仍然难以捉摸。这项研究旨在通过检查精子内父系印记基因的改变来阐明这一问题。

研究方法：招募了35名精液分析正常的个体，包括17名B肝炎表面抗原（HBsAg）阳性和18名阴性个体。本研究在前人研究的基础上，结合人类孟德尔遗传数据库（OMIM，https://www.omim.org/），对28个与多种疾病相关的父系印记基因进行了甲基化测序。

结果如下：生物信息学分析显示，19个基因内的29个CpG岛上有42个差异甲基化位点，4个基因内有4个差异甲基化CpG岛。在基因水平上，观察到DNMT 1甲基化增加，CUL7、PRKAG 2和TP 53甲基化减少。DNA甲基化单倍型分析在22个基因的36个CpG岛内鉴定出51个差异甲基化单倍型。

结论：这是第一项探讨乙型肝炎病毒感染对精子DNA甲基化的影响以及父亲乙型肝炎病毒感染代际影响的潜在潜在机制的研究。

关键词：B型肝炎病毒;印记基因;甲基化;父系;精子