乙型肝炎病毒感染者精子中父系印迹基因启动子区域的差异甲基化模式。

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

机构信息

Reproductive Medicine Center, Department of Obstetrics and Gynecology, The First Affiliated Hospital of Anhui Medical University, No. 218 Jixi Road, Hefei, 230022, China.

NHC Key Laboratory of Study On Abnormal Gametes and Reproductive Tract (Anhui Medical University), Key Laboratory of Population Health Across Life Cycle (Anhui Medical University), Ministry of Education of the People's Republic of China, Hefei, Anhui, China.

出版信息

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

DOI:10.1186/s12860-024-00515-7

PMID:39090552

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11295637/

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.

摘要

背景

乙型肝炎病毒（HBV）感染对人类健康构成重大威胁，不仅影响受感染个体，还可能对其后代的健康产生不利影响。但导致这种现象的潜在机制仍不清楚。本研究旨在通过研究精子中父系印记基因的改变来阐明这个问题。

方法

我们招募了 35 名精液分析正常的个体，其中 17 名乙型肝炎表面抗原（HBsAg）阳性，18 名阴性。根据先前的研究和在线孟德尔遗传数据库（OMIM，https://www.omim.org/ ），我们采用靶向启动子甲基化测序技术研究了与各种疾病相关的 28 个父系印记基因。

结果

生物信息学分析显示，在 19 个基因的 29 个 CpG 岛中存在 42 个差异甲基化位点，在 4 个基因中的 4 个差异甲基化 CpG 岛中存在 4 个差异甲基化位点。在基因水平上，DNMT1 的甲基化增加，CUL7、PRKAG2 和 TP53 的甲基化减少。DNA 甲基化单倍型分析在 22 个基因的 36 个 CpG 岛中发现了 51 个差异甲基化单倍型。