孕前期母体体重指数与学龄前超重/肥胖后代：脐带血中全基因组DNA甲基化变化的潜在作用

Maternal pre-pregnancy body mass index and offspring with overweight/obesity at preschool age: The possible role of epigenome-wide DNA methylation changes in cord blood.

作者信息

Chang Ruixia, Zhang Yuanyuan, Sun Jiahong, Xu Ke, Li Chunan, Zhang Jingli, Mei Wenhua, Zhang Hongzhong, Zhang Jianduan

机构信息

Department of Maternal and Child Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Traditional Chinese Medicine Hospital, Zhuhai, Guangdong, China.

出版信息

Pediatr Obes. 2023 Jan;18(1):e12969. doi: 10.1111/ijpo.12969. Epub 2022 Sep 14.

DOI:10.1111/ijpo.12969

PMID:36102013

Abstract

BACKGROUND

Epigenome-wide association studies have identified some DNA methylation sites associated with body mass index (BMI) or obesity. Studies in the Asian population are lacking.

OBJECTIVE

To examine the association of cord blood genome-wide DNA methylation (GWDm) changes with maternal pre-pregnancy BMI and children's BMI-z score at preschool age. Additionally, we also explored the genome-wide differentially methylated regions and differentially methylated probes between preschoolers with overweight/obesity and normal-weight counterparts.

METHODS

This two-stage study design included (1) a GWDm analysis of 30 mother-child pairs from 633 participants of the Zhuhai birth cohort with data on newborn cord blood, maternal pre-pregnancy BMI, and children's BMI at 3 years of age; and (2) a targeted validation analysis of the cord blood of ten children with overweight/obesity and ten matched controls to validate the CpG sites.

RESULTS

In the first stage, no significant CpG sites were found to be associated with children's BMI-z score at preschool age after FDR correction with the p-values of the CpG sites in FOXN3 (cg23501836) and ZNF264 (cg27437574) being close to 1 × 10 . In the second stage, a significant difference of CpG sites in AHRR (chr5:355067-355068) and FOXN3 (chr14: 89630264-89630272 and chr14: 89630387-89630388) was found between the ten children with overweight/obesity and ten controls (p < 0.05). The CpG sites in FOXN3 (chr14:89630264-89630272 and chr14:89630295-89630296) and ZNF264 (chr19: 57703104-57703107 and chr19: 57703301-57703307) were associated with children's BMI-z score; and the CpG sites in FOXN3 (chr14: 89630264-89630272 and chr14: 89630387-89630388) were associated with maternal pre-pregnancy BMI.

CONCLUSIONS

DNA methylation in FOXN3 and AHRR is associated with overweight/obesity in preschool-aged children, and the methylation in FOXN3 and ZNF264 might be associated with children's BMI-z score. FOXN3 methylation may be associated with maternal pre-pregnancy BMI, suggesting its potential role in the children's BMI-z score or overweight/obesity. Our results provide novel insights into the mechanisms of children's obesity.

摘要

背景

全表观基因组关联研究已经确定了一些与体重指数（BMI）或肥胖相关的DNA甲基化位点。但针对亚洲人群的研究较少。

目的

研究脐带血全基因组DNA甲基化（GWDm）变化与母亲孕前BMI以及学龄前儿童BMI-z评分之间的关联。此外，我们还探索了超重/肥胖学龄前儿童与正常体重儿童之间全基因组差异甲基化区域和差异甲基化探针。

方法

本两阶段研究设计包括：（1）对来自珠海出生队列633名参与者中的30对母婴进行GWDm分析，这些参与者有新生儿脐带血、母亲孕前BMI以及儿童3岁时BMI的数据；（2）对10名超重/肥胖儿童和10名匹配对照的脐带血进行靶向验证分析，以验证CpG位点。

结果

在第一阶段，经错误发现率（FDR）校正后，未发现与学龄前儿童BMI-z评分显著相关的CpG位点，FOXN3（cg23501836）和ZNF264（cg27437574）中CpG位点的p值接近1×10 。在第二阶段，发现10名超重/肥胖儿童与10名对照之间，芳香烃受体阻遏蛋白（AHRR，chr5:355067 - 355068）和FOXN3（chr14: 89630264 - 89630272以及chr14: 89630387 - 89630388）中的CpG位点存在显著差异（p < 0.05）。FOXN3（chr14:89630264 - 89630272以及chr14:89630295 - 89630296）和ZNF264（chr19: 57703104 - 57703107以及chr19: 57703301 - 57703307）中的CpG位点与儿童BMI-z评分相关；FOXN3（chr14: 89630264 - 89630272以及chr14: 89630387 - 89630388）中的CpG位点与母亲孕前BMI相关。