母亲孕前体重指数和学龄前超重/肥胖的后代:脐带血表观基因组DNA甲基化变化的可能作用

IF 2.7 3区医学 Q1 PEDIATRICS

Pediatric Obesity Pub Date : 2022-09-14 DOI:10.1111/ijpo.12969

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

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引用次数: 1

摘要

全表观基因组关联研究已经发现了一些与体重指数(BMI)或肥胖相关的DNA甲基化位点。目前还缺乏针对亚洲人群的研究。目的探讨脐带血全基因组DNA甲基化(GWDm)变化与母亲孕前BMI和学龄前儿童BMI-z评分的关系。此外，我们还探索了超重/肥胖学龄前儿童与正常体重学龄前儿童之间的全基因组差异甲基化区域和差异甲基化探针。方法采用两阶段研究设计:(1)对珠海出生队列633名参与者的30对母子进行GWDm分析，收集新生儿脐带血、孕妇孕前BMI和3岁儿童BMI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针对性验证分析，以验证CpG位点。结果FDR校正后，第一阶段未发现CpG位点与学龄前儿童BMI-z评分有显著相关性，FOXN3 (cg23501836)和ZNF264 (cg27437574) CpG位点的p值接近1 × 10−6。在第二阶段，10名超重/肥胖儿童的AHRR (chr5:355067-355068)和FOXN3 (chr14: 89630264-89630272和chr14: 89630387-89630388)的CpG位点与10名对照组存在显著差异(p < 0.05)。CpG位点FOXN3 (chr14:89630264-89630272和chr14:89630295-89630296)和ZNF264 (chr19: 57703104-57703107和chr19: 57703301-57703307)与儿童BMI-z评分相关;FOXN3的CpG位点(chr14: 89630264-89630272和chr14: 89630387-89630388)与孕妇孕前BMI相关。结论FOXN3和AHRR基因甲基化与学龄前儿童超重/肥胖相关，FOXN3和ZNF264基因甲基化可能与儿童BMI-z评分相关。FOXN3甲基化可能与孕妇孕前BMI有关，提示其在儿童BMI-z评分或超重/肥胖中的潜在作用。我们的研究结果为儿童肥胖的机制提供了新的见解。

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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

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 × 10⁻⁶. 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.

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来源期刊

Pediatric Obesity PEDIATRICS-

CiteScore

7.30

自引率

5.30%

发文量

117

审稿时长

6-12 weeks

期刊介绍： Pediatric Obesity is a peer-reviewed, monthly journal devoted to research into obesity during childhood and adolescence. The topic is currently at the centre of intense interest in the scientific community, and is of increasing concern to health policy-makers and the public at large. Pediatric Obesity has established itself as the leading journal for high quality papers in this field, including, but not limited to, the following: Genetic, molecular, biochemical and physiological aspects of obesity – basic, applied and clinical studies relating to mechanisms of the development of obesity throughout the life course and the consequent effects of obesity on health outcomes Metabolic consequences of child and adolescent obesity Epidemiological and population-based studies of child and adolescent overweight and obesity Measurement and diagnostic issues in assessing child and adolescent adiposity, physical activity and nutrition Clinical management of children and adolescents with obesity including studies of treatment and prevention Co-morbidities linked to child and adolescent obesity – mechanisms, assessment, and treatment Life-cycle factors eg familial, intrauterine and developmental aspects of child and adolescent obesity Nutrition security and the "double burden" of obesity and malnutrition Health promotion strategies around the issues of obesity, nutrition and physical activity in children and adolescents Community and public health measures to prevent overweight and obesity in children and adolescents.