一项试验性研究表明，在怀孕期间暴露于母体HBV感染的后代

StephenW

Gene. 2018 Mar 8. pii: S0378-1119(18)30263-4. doi: 10.1016/j.gene.2018.03.025. [Epub ahead of print]
Epigenome-wide study for the offspring exposed to maternal HBV infection during pregnancy, a pilot study.
Cheng Q1, Zhao B1, Huang Z1, Su Y1, Chen B2, Yang S2, Peng X1, Ma Q3, Yu X1, Zhao B4, Ke X5.
Author information

1
    State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Public Health, Xiamen University, Fujian, China.
2
    Women and Children's medical center, Siming District, Xiamen, Fujian, China.
3
    Neurology Department, the First Affiliated Hospital of Xiamen University, Xiamen, Fujian, China.
4
    State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Public Health, Xiamen University, Fujian, China. Electronic address: [email protected].
5
    State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Public Health, Xiamen University, Fujian, China. Electronic address: [email protected].

Abstract
BACKGROUND & AIM:

Hepatitis B virus (HBV) can be transmitted to infants, and is related to infants' later disease risk. Epigenetic change (such as DNA methylation) may be mechanism underlying the relationship. In this study, we aimed to investigate whether prenatal HBV infection could alter DNA methylation status in newborns.
METHOD:

We selected 12 neonates with intrauterine HBV infection whose mothers were HBsAg-positive during pregnancy, relative to 12 HBV-free neonates with HBsAg-negative mothers. The pattern of genome-wide DNA methylation in the umbilical cord blood was investigated by Illumina Infinium Human Methylation 450 K BeadChip.
RESULT:

The average level of global methylation in infected neonates exposed to maternal HBV infection was not significantly different from controls. However, after adjusting for multiple comparisons, we found differential significance in the cases group compared to the controls for 663 CpG sites, associated with 534 genes. Among these sites, 53.85% (357/663) had decreased methylation (ΔM < 0) and 46.15% (306/663) had increased methylation (ΔM > 0). The average percentage change (Δβ) in methylation ranged from -46% to 36%. Validated by pyrosequencing, we identified 4 significantly differentially methylated CpG sites in the KLHL35 gene and additional CpGs for the CPT1B gene. These genes play a role in the development of hepatocellular and colorectal carcinoma and fatty acid oxidation, suggesting the candidature of these genes in HBV related disease.
CONCLUSION:

Prenatal HBV exposure, even without malformation or preterm birth, may alter the epigenome profile in newborns. We identified a set of genes with differentially methylated CpG sites presented in the cord blood of HBV-infected newborns with HBsAg-positive mothers, demonstrating that DNA methylation status at birth can be used as a biomarker of prenatal exposure. These DNA methylation differences suggest a possible role for epigenetic processes in neonatal development in response to prenatal HBV exposure.

Copyright © 2017. Published by Elsevier B.V.
KEYWORDS:

DNA methylation; Human methylation 450 Beadchip; Prenatal HBV infection

PMID:
    29526602
DOI:
    10.1016/j.gene.2018.03.025

StephenW

基因。 2018年3月8日，pii：S0378-1119（18）30263-4。 doi：10.1016 / j.gene.2018.03.025。 [电子版提前打印]
一项试验性研究表明，在怀孕期间暴露于母体HBV感染的后代的表观遗传学研究。
Cheng Q1，Zhao B1，Huang Z1，Su Y1，Chen B2，Yang S2，Peng X1，Ma Q3，Yu X1，Zhao B4，Ke X5。
作者信息

1
    厦门大学公共卫生学院分子疫苗与分子诊断国家重点实验室。
2
    厦门思明区妇女儿童医疗中心，福建厦门。
3
    厦门大学第一附属医院神经内科，福建厦门。
4
    厦门大学公共卫生学院分子疫苗与分子诊断国家重点实验室。电子地址：[email protected]。
五
    厦门大学公共卫生学院分子疫苗与分子诊断国家重点实验室。电子地址：[email protected]。

抽象
背景与目的：

乙型肝炎病毒（HBV）可以传播给婴儿，并且与婴儿后期的疾病风险有关。表观遗传变化（如DNA甲基化）可能是这种关系的基础。在这项研究中，我们旨在调查产前HBV感染是否可以改变新生儿的DNA甲基化状态。
方法：

我们选择了12例宫内HBV感染的新生儿，其母亲在妊娠期间为HBsAg阳性，相对于HBsAg阴性母亲的12例不含HBV的新生儿。 Illumina Infinium Human Methylation 450K BeadChip研究了脐带血中全基因组DNA甲基化的模式。
结果：

感染母体HBV感染的新生儿的全球甲基化水平与对照组无显着差异。然而，在对多重比较进行调整后，我们发现病例组与533个基因相关的663个CpG位点的对照相比具有差异显着性。在这些位点中，53.85％（357/663）甲基化水平降低（ΔM<0），46.15％（306/663）甲基化水平升高（ΔM> 0）。甲基化的平均百分比变化（Δβ）为-46％至36％。通过焦磷酸测序验证，我们鉴定了KLHL35基因中的4个显着差异甲基化的CpG位点以及CPT1B基因的另外的CpG。这些基因在肝细胞癌和结直肠癌的发展以及脂肪酸氧化中发挥作用，表明这些基因在HBV相关疾病中的候选。
结论：

产前HBV暴露，即使没有畸形或早产，也可能改变新生儿的表观基因组谱。我们发现了一组具有HBsAg阳性母亲的HBV感染新生儿脐带血中存在差异甲基化CpG位点的基因，表明出生时DNA甲基化状态可以用作产前暴露的生物标志物。这些DNA甲基化的差异表明表观遗传过程在产前HBV暴露的新生儿发育中可能发挥作用。

版权©2017.由Elsevier B.V.出版
关键词：

DNA甲基化;人类甲基化450 Beadchip;产前HBV感染

结论：
    29526602
DOI：
    10.1016 / j.gene.2018.03.025