Prenatal tobacco smoke exposure is associated with childhood DNA CpG methylation.
Prenatal tobacco smoke exposure is associated with childhood DNA CpG methylation.
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DOI：
10.1371/journal.pone.0099716
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Asthma BRIDGE consortium
中科院分区：
文献类型：
--
作者：
Breton CV;Siegmund KD;Joubert BR;Wang X;Qui W;Carey V;Nystad W;Håberg SE;Ober C;Nicolae D;Barnes KC;Martinez F;Liu A;Lemanske R;Strunk R;Weiss S;London S;Gilliland F;Raby B;Asthma BRIDGE consortium
怀孕期间吸烟与孩子的无数负面健康结果有关。一些不利影响可能是由于表观遗传修饰，尽管很少有研究详细调查这一假设。描述哮喘儿童产前吸烟暴露引起的位点特异性表观遗传修饰。使用Illumina HumanMethylation 27微阵列，我们使用来自哮喘桥儿童哮喘管理项目（CAMP）子集的全血DNA样本（n = 527），年龄5-12岁，产前吸烟暴露数据可用，估计了主要位于基因启动子中的27，578个不同DNA序列的甲基化程度。 使用β-回归，我们筛选基因座差异甲基化相关的产前吸烟暴露，调整性别，年龄和临床部位，并占FDR的多重比较。在评估的27，578个位点中，22，131个（80%）通过质量控制评估并进行了分析。65名儿童（12%）有产前吸烟史。在FDR为0.05时，我们确定了19个与产前吸烟显著相关的CpG位点，其中两个在两个独立的人群中复制。与未暴露相比，暴露与FRMD 4A（p = 0.01）和Cllorf 52（p =0.001）中平均CpG甲基化增加2%相关。 四个额外的基因，XPNPEP 1，PPEF 2，SMPD 3和PPEGN，名义上与至少一个复制组。这些数据表明，产前暴露于烟草烟雾与可重复的表观遗传变化有关，这些变化一直持续到儿童时期。然而，这些改变的基因座的生物学意义仍然未知。
Smoking while pregnant is associated with a myriad of negative health outcomes in the child. Some of the detrimental effects may be due to epigenetic modifications, although few studies have investigated this hypothesis in detail. To characterize site-specific epigenetic modifications conferred by prenatal smoking exposure within asthmatic children. Using Illumina HumanMethylation27 microarrays, we estimated the degree of methylation at 27,578 distinct DNA sequences located primarily in gene promoters using whole blood DNA samples from the Childhood Asthma Management Program (CAMP) subset of Asthma BRIDGE childhood asthmatics (n = 527) ages 5–12 with prenatal smoking exposure data available. Using beta-regression, we screened loci for differential methylation related to prenatal smoke exposure, adjusting for gender, age and clinical site, and accounting for multiple comparisons by FDR. Of 27,578 loci evaluated, 22,131 (80%) passed quality control assessment and were analyzed. Sixty-five children (12%) had a history of prenatal smoke exposure. At an FDR of 0.05, we identified 19 CpG loci significantly associated with prenatal smoke, of which two replicated in two independent populations. Exposure was associated with a 2% increase in mean CpG methylation in FRMD4A (p = 0.01) and Cllorf52 (p = 0.001) compared to no exposure. Four additional genes, XPNPEP1, PPEF2, SMPD3 and CRYGN, were nominally associated in at least one replication group. These data suggest that prenatal exposure to tobacco smoke is associated with reproducible epigenetic changes that persist well into childhood. However, the biological significance of these altered loci remains unknown.
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影响因子：
10.4
作者：
Eskenazi B;Castorina R
通讯作者：
Castorina R
DOI：
10.1164/ajrccm.163.2.2006009
发表时间：
2001-02-01
影响因子：
24.7
作者：
Gilliland, FD;Li, YF;Peters, JM
通讯作者：
Peters, JM
影响因子：
2.5
作者：
Jauniaux, Eric;Burton, Graham J.
通讯作者：
Burton, Graham J.
影响因子：
20.3
作者：
Kim, Woo Jae;Okimoto, Ross A.;Haber, Daniel A.
通讯作者：
Haber, Daniel A.
影响因子：
11.2
作者：
Goldie SJ;Mulder KW;Tan DW;Lyons SK;Sims AH;Watt FM
通讯作者：
Watt FM