DNA methylation patterns in newborns exposed to tobacco in utero.
DNA methylation patterns in newborns exposed to tobacco in utero.
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在子宫内暴露于烟草的新生儿中的DNA甲基化模式。
DOI：
10.1186/s12967-015-0384-5
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发表时间：
2015-01-27
影响因子：
7.4
通讯作者：
Lurbe E
中科院分区：
文献类型：
--
作者：
Ivorra C;Fraga MF;Bayón GF;Fernández AF;Garcia-Vicent C;Chaves FJ;Redon J;Lurbe E
母亲在怀孕期间吸烟是不良健康结果的主要危险因素。该研究的主要目的是评估子宫内烟草暴露对出生时体重适当的足月儿 DNA 甲基化的影响。二十名母婴二人均被纳入其中，这些母子均在无并发症的妊娠后且没有围产期疾病。除吸烟母亲的相关风险外，所有母亲都很健康，没有心血管危险因素。收集脐带血和母亲外周静脉血，并使用 450 K 表观基因组范围扫描 (Illumina Infinium HumanMmethylation 450BeadChip) 进行表观基因组范围关联研究，并进行调整以标准化全血中数据细胞变异性的 DNA 甲基化。暴露组的母体血浆可替宁水平范围为 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调整后，观察到与 25 个基因相关的 31 个 CpG 位点存在统计显着差异。位于 CpG 岛的具有统计显着性的位点比例高于预期（Fisher 精确检验，p = 0.029），并且在这些 CpG 岛中，90.3% 在暴露组中表现出较高的甲基化水平。最引人注目和最重要的 CpG 位点 cg05727225 位于染色体 11p15.4 的肾上腺髓质素基因内。在子宫内接触烟草，即使没有胎儿生长受限，也可能改变表观基因组，导致整体 DNA 低甲基化。因此，DNA 状态可以用作产前损伤的生物标志物。考虑到逆转表观遗传修饰的可能性，存在改变程序性慢性疾病的机会之窗。
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.
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影响因子：
10.4
作者：
Pichini, S;Basagaña, X;Sunyer, J
通讯作者：
Sunyer, J
影响因子：
6.9
作者：
Vila, Greisa;Riedl, Michaela;Luger, Anton
通讯作者：
Luger, Anton
DOI：
10.1002/bies.201300090
发表时间：
2014-01
期刊：
BioEssays : news and reviews in molecular, cellular and developmental biology
影响因子：
--
作者：
Szulwach KE;Jin P
通讯作者：
Jin P
影响因子：
9.8
作者：
Holmgren, Calla;Aagaard-Tillery, Kjersti M.;Varner, Michael
通讯作者：
Varner, Michael
影响因子：
3.1
作者：
Puig C;Vall O;García-Algar O;Papaseit E;Pichini S;Saltó E;Villalbí JR
通讯作者：
Villalbí JR