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中国足月低出生体重儿母亲血液、胎盘和脐带血中芳烃受体(AHRR)基因DNA甲基化变化的组织差异

Tissue differences in DNA methylation changes at AHRR in full term low birth weight in maternal blood, placenta and cord blood in Chinese.

作者信息

Tian Fu-Ying, Hivert Marie-France, Wen Xiaozhong, Xie Chuanbo, Niu Zhongzheng, Fan Lijun, Gillman Matthew W, Chen Wei-Qing

机构信息

Department of Medical Statistics and Epidemiology, Guangzhou Key Laboratory of Environmental Pollution and Health Assessment, Guangdong Provincial Key Laboratory of Food, Nutrition and Health, School of Public Health, Sun Yat-sen University, Guangzhou, Guangdong, China.

Department of Population Medicine, Harvard Medical School, Harvard Pilgrim Health Care Institute, 401 Park Drive, Suite 401, Boston, MA, USA; Diabetes Center, Massachusetts General Hospital, 50 Staniford Street, Boston, MA, USA; Department of Medicine, Université de Sherbrooke, 3001 12th Avenue North, Sherbrooke, Québec, Canada; Centre de recherche du Centre Hospitalier Universitaire de Sherbrooke, 3001 12th Avenue North, Wing 9, Door 6, Sherbrooke, Québec, Canada.

出版信息

Placenta. 2017 Apr;52:49-57. doi: 10.1016/j.placenta.2017.02.017. Epub 2017 Feb 17.

Abstract

INTRODUCTION

Very few study addressed the relationship between Aryl-hydrocarbon receptor repressor (AHRR) DNA methylation and low birth weight, especially in multiple tissues of mother-infant pairs. In this study, we aimed to investigate AHRR DNA methylation modification in cord blood, placenta and maternal blood between full term low birth weight (FT-LBW) and full term normal birth weight (FT-NBW) newborns.

METHODS

We enrolled 90 FT-LBW and 90 FT-NBW mother-infant pairs, of which all placenta and cord blood samples were collected while 45 maternal blood samples of each group were collected. We measured AHRR DNA methylation (Chr5: 373013-373606) using Sequenom MassARRAY, and assessed associations between AHRR DNA methylation and FT-LBW using logistic regression adjusting for maternal age, education, family income, delivery mode, and passive smoking.

RESULTS

FT-LBW babies had 3% lower methylation at Chr5: 373378 (CpG 13) in cord blood, and 4-9% higher methylation levels at Chr5: 373315, 373378, 373423, 373476 and 373490/373494 (CpG 10; 13; 15; 16; 17/18 respectively) in maternal blood, comparing with FT-NBW. The methylation of Chr5: 373378 (CpG 13) remained significant association with FT-LBW both in cord blood (OR = 0.90; 95% CI: 0.82, 0.98) and maternal blood (OR = 1.14; 95% CI: 1.04, 1.25) further adjusting for each other in the same model. We observed no significant difference at any CpG sites in placenta.

DISCUSSION

AHRR DNA methylation of cord and maternal blood might be independently associated with FT-LBW in different ways.

摘要

引言

很少有研究探讨芳烃受体阻遏物(AHRR)DNA甲基化与低出生体重之间的关系,尤其是在母婴对的多个组织中。在本研究中,我们旨在调查足月低出生体重(FT-LBW)和足月正常出生体重(FT-NBW)新生儿脐带血、胎盘和母体血液中AHRR DNA甲基化修饰情况。

方法

我们招募了90对FT-LBW母婴对和90对FT-NBW母婴对,收集了所有的胎盘和脐带血样本,同时每组收集45份母体血液样本。我们使用Sequenom MassARRAY测量AHRR DNA甲基化(Chr5: 373013 - 373606),并使用逻辑回归分析调整母亲年龄、教育程度、家庭收入、分娩方式和被动吸烟情况,评估AHRR DNA甲基化与FT-LBW之间的关联。

结果

与FT-NBW相比,FT-LBW婴儿脐带血中Chr5: 373378(CpG 13)的甲基化水平低3%,母体血液中Chr5: 373315、373378、373423、373476和373490/373494(分别为CpG 10;13;15;16;17/18)的甲基化水平高4 - 9%。在同一模型中进一步相互调整后,Chr5: 373378(CpG 13)的甲基化在脐带血(OR = 0.90;95% CI:0.82,0.98)和母体血液(OR = 1.14;95% CI:1.04,1.25)中仍与FT-LBW存在显著关联。我们在胎盘中的任何CpG位点均未观察到显著差异。

讨论

脐带血和母体血液中AHRR DNA甲基化可能以不同方式独立与FT-LBW相关。

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