Self-reported prenatal tobacco smoke exposure, AXL gene-body methylation, and childhood asthma phenotypes.
Self-reported prenatal tobacco smoke exposure, AXL gene-body methylation, and childhood asthma phenotypes.
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DOI：
10.1186/s13148-018-0532-x
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发表时间：
2018-07-20
影响因子：
5.7
通讯作者：
Breton CV
中科院分区：
文献类型：
--
作者：
Gao L;Liu X;Millstein J;Siegmund KD;Dubeau L;Maguire RL;Jim Zhang J;Fuemmeler BF;Kollins SH;Hoyo C;Murphy SK;Breton CV
表观遗传修饰，包括DNA甲基化，是产前吸烟(PTS)相关有害影响的潜在机制之一。此前有报道称，一种名为Axl的基因的甲基化程度与PTS的反应不同。我们调查了PTS和AXL的表观遗传学改变之间的关系，以及这与儿童哮喘表型之间的关系。我们在儿童健康研究(CHS，n=799)和新生儿表观遗传学研究(Nest，n=592)两个不同的研究群体中，使用焦磷酸测序技术测试了出生时AXL多个CpG基因座的PTS和DNA甲基化之间的相关性。血浆可替宁浓度被用来验证自我报告的吸烟状况的结果。分析Axl mRNA和miR-199a1表达、PTS和Ax1甲基化之间的相互关系。最后，我们评估了Axl甲基化和PTS在10岁时对哮喘风险和相关症状的联合影响。在CHS和Nest受试者中，PTS与Ax1基因体中较高的甲基化水平相关。在合并分析中，暴露的受试者在该区域的甲基化水平比未暴露的受试者高0.51%(95%可信区间0.29，0.74；p <； 0.0001)。PTS还与miR-199a1(95%CI− 37.9，− 0.1；p = 0.05)的低表达有关，miR-199a1是一种调节Ax1表达的微RNA。此外，出生时较高的Axl甲基化和PTS暴露增加了儿童时期最近发生支气管炎症状的风险。PTS与AXL的甲基化水平相关，两者的结合改变了儿童支气管炎症状的风险。本文的在线版本(10.1186/s131480180532x)包含补充材料，可供授权用户使用。
Epigenetic modifications, including DNA methylation, act as one potential mechanism underlying the detrimental effects associated with prenatal tobacco smoke (PTS) exposure. Methylation in a gene called AXL was previously reported to differ in response to PTS. We investigated the association between PTS and epigenetic changes in AXL and how this was related to childhood asthma phenotypes. We tested the association between PTS and DNA methylation at multiple CpG loci of AXL at birth using Pyrosequencing in two separate study populations, the Children’s Health Study (CHS, n = 799) and the Newborn Epigenetic Study (NEST, n = 592). Plasma cotinine concentration was used to validate findings with self-reported smoking status. The inter-relationships among AXL mRNA and miR-199a1 expression, PTS, and AXL methylation were examined. Lastly, we evaluated the joint effects of AXL methylation and PTS on the risk of asthma and related symptoms at age 10 years old. PTS was associated with higher methylation level in the AXL gene body in both CHS and NEST subjects. In the pooled analysis, exposed subjects had a 0.51% higher methylation level in this region compared to unexposed subjects (95% CI 0.29, 0.74; p < 0.0001). PTS was also associated with 21.2% lower expression of miR-199a1 (95% CI − 37.9, − 0.1; p = 0.05), a microRNA known to regulate AXL expression. Furthermore, the combination of higher AXL methylation and PTS exposure at birth increased the risk of recent episodes of bronchitic symptoms in childhood. PTS was associated with methylation level of AXL and the combination altered the risk of childhood bronchitic symptoms. The online version of this article (10.1186/s13148-018-0532-x) contains supplementary material, which is available to authorized users.
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影响因子：
3.7
作者：
Anblagan D;Jones NW;Costigan C;Parker AJ;Allcock K;Aleong R;Coyne LH;Deshpande R;Raine-Fenning N;Bugg G;Roberts N;Pausova Z;Paus T;Gowland PA
通讯作者：
Gowland PA
影响因子：
5.7
作者：
Gao L;Millstein J;Siegmund KD;Dubeau L;Maguire R;Gilliland FD;Murphy SK;Hoyo C;Breton CV
通讯作者：
Breton CV
DOI：
10.1001/archpediatrics.2012.170
发表时间：
2012-09-01
影响因子：
--
作者：
Dempsey, Delia A.;Meyers, Matthew J.;Oh, Sam S.;Nguyen, Elizabeth A.;Fuentes-Afflick, Elena;Wu, Alan H. B.;Jacob, Peyton, III;Benowitz, Neal L.
通讯作者：
Benowitz, Neal L.
DOI：
10.1164/rccm.2111021
发表时间：
2002-07-01
影响因子：
24.7
作者：
Gauderman, WJ;Gilliland, GF;Peters, JM
通讯作者：
Peters, JM
影响因子：
4.7
作者：
Bernert, John T.;Jacob, Peyton, III;Langman, Loralie J.
通讯作者：
Langman, Loralie J.