产前铅暴露与韩国外显子组研究中的脐带血 DNA 甲基化。

Prenatal lead exposure and cord blood DNA methylation in the Korean Exposome Study.

机构信息

Interdisciplinary Program of Bioinformatics, College of Natural Sciences, Seoul National University, Seoul, South Korea.

Department of Internal Medicine and Environmental Health Center, Kangwon National University, Chuncheon, South Korea.

出版信息

Environ Res. 2021 Apr;195:110767. doi: 10.1016/j.envres.2021.110767. Epub 2021 Jan 28.

DOI:10.1016/j.envres.2021.110767

PMID:33515580

Abstract

BACKGROUND

Prenatal lead exposure has been reported to affect infant growth and nervous system development, as well as to influence DNA methylation. We conducted an epigenome-wide association study to identify associations between prenatal lead exposure and cord blood DNA methylation in Korean infants.

METHODS

Cord blood samples were assayed with the Illumina HumanMethylationEPIC BeadChip kits, and maternal blood lead levels during early and late pregnancy, as well as cord blood lead level, were measured. The association between CpG methylation and lead level was analyzed using the limma package, with adjusting for infant sex, maternal pre-pregnancy body mass index, and estimated leukocyte composition.

RESULTS

Among 364 blood samples (182 males and 182 females), those for which maternal and cord blood lead concentrations during early and later pregnancy was known were used for analysis. Maternal lead concentration in blood during early pregnancy was significantly associated with the methylation status of specific positions. After data stratification by infant sex, we found that, in males, the level of maternal blood lead was associated with 18 CpG sites during early pregnancy, and with one CpG site near the NBAS gene, during late pregnancy. In female samples, there was no significant association between DNA methylation and lead concentrations.

CONCLUSIONS

Prenatal lead exposure was associated with altered, gender-specific patterns of DNA methylation in Korean infants.

摘要

背景

已有研究报道，产前铅暴露会影响婴儿的生长和神经系统发育，并影响 DNA 甲基化。我们开展了一项全基因组关联研究，以鉴定韩国婴儿脐带血中产前铅暴露与 DNA 甲基化之间的关联。

方法

采用 Illumina HumanMethylationEPIC BeadChip 试剂盒检测脐带血样本，并检测孕早期和孕晚期母亲血液中的铅水平以及脐带血中的铅水平。采用 limma 包分析 CpG 甲基化与铅水平之间的关联，并调整婴儿性别、母亲孕前体重指数和估计的白细胞组成。

结果

在 364 份血样（182 名男性和 182 名女性）中，选取了已知母亲和脐带血在孕早期和孕晚期铅浓度的样本进行分析。孕早期母亲血液中的铅浓度与特定位置的甲基化状态显著相关。在按婴儿性别对数据进行分层后，我们发现，在男性中，母亲血液中的铅水平与孕早期的 18 个 CpG 位点以及孕晚期的 NBAS 基因附近的一个 CpG 位点有关。在女性样本中，DNA 甲基化与铅浓度之间没有显著关联。