...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Environmental health perspectives. >DNA Methylation in Babies Born to Nonsmoking Mothers Exposed to Secondhand Smoke during Pregnancy: An Epigenome-Wide Association Study
【24h】

DNA Methylation in Babies Born to Nonsmoking Mothers Exposed to Secondhand Smoke during Pregnancy: An Epigenome-Wide Association Study

机译：在怀孕期间出生于非莫斯莫氏母亲的婴儿的DNA甲基化：外延一致的协会研究

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

摘要

Background: Maternal smoking during pregnancy is related to altered DNA methylation in infant umbilical cord blood. The extent to which low levels of smoke exposure among nonsmoking pregnant women relates to offspring DNA methylation is unknown. Objective: This study sought to evaluate relationships between maternal prenatal plasma cotinine levels and DNA methylation in umbilical cord blood in newborns using the Infinium HumanMethylation 450K BeadChip. Methods: Participants from the Newborn Epigenetics Study cohort who reported not smoking during pregnancy had verified low levels of cotinine from maternal prenatal plasma (0 ng / mL to 4 ng / mL ), and offspring epigenetic data from umbilical cord blood were included in this study ( n = 79 ). Multivariable linear regression models were fit to the data, controlling for cell proportions, age, race, education, and parity. Estimates represent changes in response to any 1 -ng / mL unit increase in exposure. Results: Multivariable linear regression models yielded 29,049 CpGs that were differentially methylated in relation to increases in cotinine at a 5% false discovery rate. Top CpGs were within or near genes involved in neuronal functioning ( PRKG1 , DLGAP2 , BSG ), carcinogenesis ( FHIT , HSPC157 ) and inflammation ( AGER ). Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses suggest cotinine was related to methylation of gene pathways controlling neuronal signaling, metabolic regulation, cell signaling and regulation, and cancer. Further, enhancers associated with transcription start sites were enriched in altered CpGs. Using an independent sample from the same study population ( n = 115 ), bisulfite pyrosequencing was performed with infant cord blood DNA for two genes within our top 20 hits ( AGER and PRKG1 ). Results from pyrosequencing replicated epigenome results for PRKG1 (cg17079497, estimate = ? 1.09 , standard error ( SE ) = 0.45 , p = 0.018 ) but not for AGER (cg09199225; estimate = ? 0.16 , SE = 0.21 , p = 0.44 ). Discussion: Secondhand smoke exposure among nonsmoking women may alter DNA methylation in regions involved in development, carcinogenesis, and neuronal functioning. These novel findings suggest that even low levels of smoke exposure during pregnancy may be sufficient to alter DNA methylation in distinct sites of mixed umbilical cord blood leukocytes in pathways that are known to be altered in cord blood from pregnant active smokers.
机译：背景：妊娠期间的母亲吸烟与婴儿脐带血中的DNA甲基化改变有关。非莫斯汀孕妇中烟雾暴露程度的程度涉及后代DNA甲基化是未知的。目的：本研究试图评估新生儿450K珠芯片在新生儿中脐带血中母体产前血浆胞苷水平和DNA甲基化之间的关系。方法：从妊娠期间尚未吸烟的新生目观生物学研究队列的参与者已从母体产前血浆（0 ng / ml至4ng / ml）中验证了低水平的胞苷，并且包括来自脐带血的后代表观遗传数据这项研究（n = 79）。多变量线性回归模型适合数据，控制细胞比例，年龄，种族，教育和平价。估计表示响应任何1-NG / mL单位的暴露增加的变化。结果：多变量线性回归模型产生29,049个CPG，差异甲基化，以含有5％的假发现率的胞苷增加。顶部CPG在涉及神经元功能（PRKG1，DLGAP2，BSG），致癌（FHIT，HSPC157）和炎症（患者）中的基因内或附近。基因和基因组（Kegg）分析的京都百科全书建议胞苷与控制神经元信号，代谢调节，细胞信号传导和癌症的基因途径的甲基化有关。此外，与转录起始位点相关的增强剂在改变的CpG中富集。使用来自同一研究人群（n = 115）的独立样品，用婴儿脐带血DNA进行二硫酸氢盐焦磷酸，用于我们前20名击中（肌肉和PRKG1）。 Pyrosequencing的结果对PRKG1（CG17079497，估计=Δ1.09，标准误差（SE）= 0.45，P = 0.018）但不适用于Ager（CG09199225;估计= 0.16，SE = 0.21，P = 0.44）。讨论：非莫斯文中的二手烟雾暴露可能会在参与开发，致癌物和神经元功能的区域中改变DNA甲基化。这些新发现表明，妊娠期间的烟雾暴露水平甚至可能足以改变在已知的患者中已知的途径中的混合脐带血白细胞细胞的不同位点中的DNA甲基化。

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