Global DNA hypomethylation is associated with in utero exposure to cotinine and perfluorinated alkyl compounds
Global DNA hypomethylation is associated with in utero exposure to cotinine and perfluorinated alkyl compounds
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DOI：
10.4161/epi.5.6.12378
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发表时间：
2010-08-16
期刊：
影响因子：
3.7
通讯作者：
Sidransky, David
中科院分区：
文献类型：
--
作者：
Guerrero-Preston, Rafael;Goldman, Lynn R.;Sidransky, David
子宫内的环境暴露可能会改变表观基因组，从而影响染色体稳定性和基因表达。我们假设，在子宫内暴露于母亲吸烟和全氟烷基化合物 (PFC) 与脐带血清中整体 DNA 低甲基化有关。我们的目标是确定全局 DNA 甲基化是否可以用作子宫内母亲吸烟和 PFC 暴露的生物标志物。使用基于 ELISA 的方法，对 30 名脐带血清可替宁水平高（> 10 ng/ml，平均 123.8 ng/ml）、低（范围 1-10 ng/ml，平均 1.6 ng/ml）和极低（< 1 ng/ml，平均 0.06 ng/ml）新生儿的脐带血清中的整体 DNA 甲基化进行了定量。进行 Y 染色体分析以排除母体 DNA 交叉污染。脐带血清整体 DNA 甲基化显示与血清可替宁水平呈反向剂量反应 (p < 0.001)。与二手烟母亲 (21.1%; 95% CI, 16.6, 25.5) 和不吸烟母亲 (平均 = 29.2%; 95% CI, 20.1) 的婴儿相比，吸烟母亲的新生儿脐带血中的总体 DNA 甲基化水平最低 (平均 = 15.04%; 95% CI, 8.4, 21.7)。 38.1）。整体 DNA 甲基化与血清 PFOA 呈负相关（r = -0.35，p = 0.06），但与 PFOS 水平无关。血清 Y 染色体分析未检测到母体 DNA 交叉污染。这项研究支持使用整体 DNA 甲基化状态作为子宫内暴露于香烟烟雾和 PFC 的生物标志物。
Environmental exposures in utero may alter the epigenome, thus impacting chromosomal stability and gene expression. We hypothesized that in utero exposures to maternal smoking and perfluoroalkyl compounds (PFCs) are associated with global DNA hypomethylation in umbilical cord serum. Our objective was to determine if global DNA methylation could be used as a biomarker of in utero exposures to maternal smoking and PFCs. Using an ELISA-based method, global DNA methylation was quantified in umbilical cord serum from 30 newborns with high (> 10 ng/ml, mean 123.8 ng/ml), low (range 1-10 ng/ml, mean 1.6 ng/ml) and very low (< 1 ng/ml, mean 0.06 ng/ml) cord serum cotinine levels. Y chromosome analysis was performed to rule out maternal DNA cross-contamination. Cord serum global DNA methylation showed an inverse dose response to serum cotinine levels (p < 0.001). Global DNA methylation levels in cord blood were the lowest among newborns with smoking mothers (mean = 15.04%; 95% CI, 8.4, 21.7) when compared to babies of mothers who were second-hand smokers (21.1%; 95% CI, 16.6, 25.5) and non-smokers (mean = 29.2%; 95% CI, 20.1, 38.1). Global DNA methylation was inversely correlated with serum PFOA (r = -0.35, p = 0.06) but not PFOS levels. Serum Y chromosome analyses did not detect maternal DNA cross-contamination. This study supports the use of global DNA methylation status as a biomarker of in utero exposure to cigarette smoke and PFCs.