Maternal smoking and DNA methylation in newborns: in utero effect or epigenetic inheritance?
Maternal smoking and DNA methylation in newborns: in utero effect or epigenetic inheritance?
复制标题
DOI：
10.1158/1055-9965.epi-13-1256
复制
发表时间：
2014-06
期刊：
影响因子：
--
通讯作者：
London SJ
中科院分区：
文献类型：
--
作者：
Joubert BR;Håberg SE;Bell DA;Nilsen RM;Vollset SE;Midttun O;Ueland PM;Wu MC;Nystad W;Peddada SD;London SJ
孕期母亲吸烟与儿童的不良健康后果有关，包括癌症；潜在的机制可能包括表观遗传修饰。使用Illumina的450K阵列，我们先前在挪威母子队列研究(MoBA)的新生儿脐带血中的10个基因的26个CpG位点(CPG)上发现了与怀孕期间母亲吸烟有关的差异DNA甲基化。目前尚不清楚新生儿中的这些甲基化信号是否仅反映在子宫暴露中，或者可能是吸烟相关修饰的表观遗传。因此，我们评估了母亲吸烟的时机(怀孕前或怀孕期间使用怀孕18周时测量的可替宁)、父亲在受孕前吸烟以及祖母在怀孕期间与母亲一起吸烟对1,042名MoBA新生儿这26个CPGS甲基化的影响。我们使用稳健线性回归，调整协变量，应用Bonferroni校正。观察到母亲在孕期至少18周期间持续吸烟的相关性最强且仅有统计学意义(p<；所有26个Cpg均为1.6×10−5)。我们没有观察到由于母亲怀孕前吸烟或18周后停止吸烟、父亲在怀孕前吸烟或祖母在母亲怀孕期间吸烟而导致的甲基化差异无统计学意义。在新生儿中，这些CPGS的不同甲基化似乎反映了宫内持续暴露，而不是表观遗传。怀孕早期戒烟可能会抵消甲基化的影响。对母亲怀孕期间吸烟和子女健康后果(包括癌症)的分析，仅限于曾经吸烟，可能会错过真正的联系。
Maternal smoking in pregnancy is associated with adverse health outcomes in children, including cancers; underlying mechanisms may include epigenetic modifications. Using Illumina’s 450K array, we previously identified differential DNA methylation related to maternal smoking during pregnancy at 26 CpG sites (CpGs) in 10 genes in newborn cord bloods from the Norwegian Mother and Child Cohort Study (MoBa). Whether these methylation signals in newborns reflect in utero exposure only or possibly epigenetic inheritance of smoking-related modifications is unclear. We therefore evaluated the impact of the timing of mother’s smoking (before or during pregnancy using cotinine measured at 18 weeks gestation), the father’s smoking before conception, and the grandmother’s smoking during her pregnancy with the mother on methylation at these 26 CpGs in 1,042 MoBa newborns. We used robust linear regression, adjusting for covariates, applying Bonferroni correction. The strongest and only statistically significant associations were observed for sustained smoking by the mother during pregnancy through at least gestational week 18 (p<1.6×10−5 for all 26 CpGs). We observed no statistically significant differential methylation due to smoking by the mother prior to pregnancy or that ceased by week 18, father’s smoking before conception, or grandmother’s smoking while pregnant with the mother. Differential methylation at these CpGs in newborns appears to reflect sustained in utero exposure rather than epigenetic inheritance. Smoking cessation in early pregnancy may negate effects on methylation. Analyses of maternal smoking during pregnancy and offspring health outcomes, including cancer, limited to ever smoking might miss true associations.