Ivorra Carmen, Fraga Mario F, Bayón Gustavo F, Fernández Agustín F, Garcia-Vicent Consuelo, Chaves F Javier, Redon Josep, Lurbe Empar
Pediatrics Department, Consorcio Hospital General, University of Valencia, Valencia, Spain.
CIBER Fisiopatología Obesidad y Nutrición (CB06/03), Instituto de Salud Carlos III, Madrid, Spain.
J Transl Med. 2015 Jan 27;13:25. doi: 10.1186/s12967-015-0384-5.
Maternal smoking during pregnancy is a major risk factor for adverse health outcomes. The main objective of the study was to assess the impact of in utero tobacco exposure on DNA methylation in children born at term with appropriate weight at birth.
Twenty mother-newborn dyads, after uncomplicated pregnancies, in the absence of perinatal illness were included. All mothers were healthy with no cardiovascular risk factors, except for the associated risks among those mothers who smoked. Umbilical cord blood and maternal peripheral venous blood were collected and an epigenome-wide association study was performed using a 450 K epigenome-wide scan (Illumina Infinium HumanMethylation 450BeadChip) with adjustment to normalize the DNA methylation for data cell variability in whole blood.
The maternal plasmatic cotinine levels ranged from 10.70-115.40 ng/ml in the exposed group to 0-0.59 ng/ml in the non-exposed group. After adjusting for multiple comparisons in 427102 probes, statistically significant differences for 31 CpG sites, associated to 25 genes were observed. There was a greater than expected proportion of statistically-significant loci located in CpG islands (Fisher's exact test, p = 0.029) and of those CpG islands, 90.3% exhibit higher methylation levels in the exposed group. The most striking and significant CpG site, cg05727225, is located in the chromosome 11p15.4, within the adrenomedullin gene.
In utero tobacco exposure, even in the absence of fetal growth restriction, may alter the epigenome, contributing to global DNA hypomethylation. Therefore, DNA status can be used as a biomarker of prenatal insults. Considering the possibility to reverse epigenetic modifications, a window of opportunity exists to change the programmed chronic disease.
孕期母亲吸烟是不良健康结局的主要危险因素。本研究的主要目的是评估子宫内烟草暴露对足月出生且出生体重正常的儿童DNA甲基化的影响。
纳入20对母婴二元组，其孕期无并发症，无围产期疾病。所有母亲均健康，无心血管危险因素，但吸烟母亲存在相关风险。采集脐带血和母亲外周静脉血，并使用450K全基因组扫描（Illumina Infinium HumanMethylation 450BeadChip）进行全基因组关联研究，并进行调整以标准化全血中数据细胞变异性的DNA甲基化。
暴露组母亲血浆可替宁水平为10.70 - 115.40 ng/ml，非暴露组为0 - 0.59 ng/ml。在对427102个探针进行多重比较校正后，观察到与25个基因相关的31个CpG位点存在统计学显著差异。位于CpG岛的统计学显著位点比例高于预期（Fisher精确检验，p = 0.029），在这些CpG岛中，90.3%在暴露组中表现出更高的甲基化水平。最显著的CpG位点cg05727225位于11号染色体p15.
