• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文会议>Annual conference of the International Society of Exposure Science >Epigenetic effects of intrauterine exposure to persistent organic pollutants, the INMA birth cohort
【24h】

Epigenetic effects of intrauterine exposure to persistent organic pollutants, the INMA birth cohort

机译：宫内暴露于持久性有机污染物的表观遗传学影响，INMA出生队列

获取原文
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Background: Prenatal environment can be recorded in offspring as changes in epigenetic marks. Aims: In the INfancia y Medio Ambiente (INMA) Project, we have investigated: 1) cord blood gene specific DNA methylation changes in relation to prenatal dichlorodiphenyldichloroethylene (ODE) exposure and risk of asthma-related phenotypes, and 2) placental changes in global DNA methylation in relation to prenatal exposure to xenoestrogens. Results: In the first study, the discovery phase using the Illumina GoldenGate Panel I identified lower DNA methylation at a CpG site in the arachidonate 12-lipoxygenase (ALOX12) gene in children having persistent wheezing compared with those never wheezed at age 6 years in the INMA Menorca cohort (p=0.003). Pyrosequencing confirmed that DNA hypomethylation at ALOX12 loci was associated with higher risk of persistent wheezing in the INMA Menorca cohort (OR per 1% methylation decrease, 1.13; 95% CI, 0.99-1.29; p= 0.077) and in the INMA Sabadell cohort (OR, 1.16; 95% CI, 1.03-1.37; p=0.017). Higher levels of prenatal DDE, previously associated with risk of persistent wheezing, were associated with DNA hypomethylation of ALOX12 in the Menorca cohort (p=0.033), but not in the Sabadell cohort (p=0.377). ALOX12 DNA methylation was strongly determined by underlying genetic polymorphisms. In the second study, total effective xenoestrogen burden (TEXB) was measured in placenta (n=200, 50% males). The % of DNA 5mC was analyzed on 10 different repetitive elements (4 LINEs, 3 Alus and 3 HERVs) per duplicate by bisulfite pyrosequencing. One to five CpG sites were analyzed and average methylation levels were regressed over tertiles of TEXB levels. After adjustment, higher TEXB levels (3rd vs. 1st tertile) were associated with an increase in methylation of 1.2% in one of the LINE1 elements (L1PA5) (p ＜0.001), without significant sex interactions. Conclusions: Assessment of epigenetic marks in offspring could help to unravel mechanisms underlying adverse effects of chemical exposures in development.
机译：背景：产后环境可以在后代中记录为表观遗传标记的变化。目的：在INfancia y Medio Ambiente（INMA）项目中，我们进行了以下研究：1）脐血基因特定的DNA甲基化变化与产前二氯二苯基二氯乙烯（ODE）暴露和哮喘相关表型的风险有关，以及2）胎盘在全球范围内的变化DNA甲基化与产前暴露于异雌激素有关。结果：在第一项研究中，使用Illumina GoldenGate专家组I的发现阶段发现患有持续性喘息的儿童与6岁时从未喘息的儿童相比，花生四烯酸12-脂加氧酶（ALOX12）基因CpG位点的DNA甲基化程度较低。 INMA Menorca队列（p = 0.003）。焦磷酸测序证实，ALOX12基因座处的DNA低甲基化与INMA Menorca队列中持续性喘息的风险较高（或每1％甲基化降低，1.13; 95％CI，0.99-1.29; p = 0.077）和INMA Sabadell队列中（ OR，1.16; 95％CI，1.03-1.37; p = 0.017）。在梅诺卡岛队列中，较高水平的产前DDE与先前存在持续性喘息的风险有关，与ALOX12的DNA低甲基化有关（p = 0.033），而在萨瓦德尔队列中则没有（AL = 0.377）。 ALOX12 DNA甲基化很大程度上取决于潜在的遗传多态性。在第二项研究中，在胎盘（n = 200，男性占50％）中测量了总有效异种雌激素负荷（TEXB）。通过亚硫酸氢盐焦磷酸测序对每个重复样本的10个不同重复元素（4个LINE，3个Alus和3个HERV）分析DNA 5mC的百分比。分析了1至5个CpG位点，并在TEXB水平的三分位数上回归了平均甲基化水平。调整后，较高的TEXB水平（第3位对第1位）与LINE1元素之一（L1PA5）的甲基化增加1.2％（p ＜0.001）相关，而没有明显的性别相互作用。结论：评估后代的表观遗传标记可以帮助揭示潜在的化学暴露对发育的不良影响的机制。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号