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脐带血甲基化与新生儿瘦素的关联:一项全基因组甲基化关联研究。

Association of cord blood methylation with neonatal leptin: An epigenome wide association study.

机构信息

Division of Endocrinology, Ann and Robert H. Lurie Children's Hospital of Chicago and Department of Pediatrics, Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States of America.

Center for Population Epigenetics, Robert H. Lurie Comprehensive Cancer Center and Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States of America.

出版信息

PLoS One. 2019 Dec 18;14(12):e0226555. doi: 10.1371/journal.pone.0226555. eCollection 2019.

Abstract

BACKGROUND

Neonatal adiposity is a risk factor for childhood obesity. Investigating contributors to neonatal adiposity is important for understanding early life obesity risk. Epigenetic changes of metabolic genes in cord blood may contribute to excessive neonatal adiposity and subsequent childhood obesity. This study aims to evaluate the association of cord blood DNA methylation patterns with anthropometric measures and cord blood leptin, a biomarker of neonatal adiposity.

METHODS

A cross-sectional study was performed on a multiethnic cohort of 114 full term neonates born to mothers without gestational diabetes at a university hospital. Cord blood was assayed for leptin and for epigenome-wide DNA methylation profiles via the Illumina 450K platform. Neonatal body composition was measured by air displacement plethysmography. Multivariable linear regression was used to analyze associations between individual CpG sites as well as differentially methylated regions in cord blood DNA with measures of newborn adiposity including anthropometrics (birth weight, fat mass and percent body fat) and cord blood leptin. False discovery rate was estimated to account for multiple comparisons.

RESULTS

247 CpG sites as well as 18 differentially methylated gene regions were associated with cord blood leptin but no epigenetic changes were associated with birth weight, fat mass or percent body fat. Genes of interest identified in this study are DNAJA4, TFR2, SMAD3, PLAG1, FGF1, and HNF4A.

CONCLUSION

Epigenetic changes in cord blood DNA are associated with cord blood leptin levels, a measure of neonatal adiposity.

摘要

背景

新生儿肥胖是儿童肥胖的一个危险因素。研究新生儿肥胖的原因对于了解早期生命肥胖风险很重要。脐带血中代谢基因的表观遗传变化可能导致新生儿肥胖和随后的儿童肥胖。本研究旨在评估脐带血 DNA 甲基化模式与人体测量指标和脐带血瘦素(一种衡量新生儿肥胖的生物标志物)之间的关系。

方法

对一家大学医院的多民族队列中 114 名无妊娠糖尿病的母亲所生的足月新生儿进行了一项横断面研究。通过 Illumina 450K 平台检测脐带血瘦素和全基因组 DNA 甲基化谱。通过空气置换体描记法测量新生儿的身体成分。多变量线性回归用于分析脐带血 DNA 中单个 CpG 位点以及差异甲基化区域与新生儿肥胖指标(包括人体测量指标、出生体重、脂肪量和体脂百分比)和脐带血瘦素之间的关系。假发现率估计用于校正多重比较。

结果

247 个 CpG 位点和 18 个差异甲基化基因区域与脐带血瘦素相关,但没有表观遗传变化与出生体重、脂肪量或体脂百分比相关。本研究中确定的感兴趣基因包括 DNAJA4、TFR2、SMAD3、PLAG1、FGF1 和 HNF4A。

结论

脐带血 DNA 的表观遗传变化与脐带血瘦素水平相关,瘦素是衡量新生儿肥胖的指标。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e9ca/6919608/4f1b8110f6ef/pone.0226555.g001.jpg

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