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DNA Methylation and Exposure to Multiple Metals during Pregnancy among Women Living near a Superfund Site

机译:居住在超级基金所在地附近的妇女在怀孕期间的DNA甲基化和多种金属的暴露

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Background: Evidence suggests that metals may influence epigenetic phenomena, such as DNA methylation, which regulate gene expression. Early life exposures may program later disease outcomes, thus, pregnancy is an important period of interest for studying these relationships. Aims: To evaluate DNA methylation and exposure to multiple metals during pregnancy among women living near the Tar Creek Superfund site in Oklahoma (USA). Methods: We used PCR-Pyrosequencing~® to quantify global methylation inAlu andLINE-1 repetitive elements in bisulfite-treated DNA derived from peripheral blood leukocytes of 167 women. Gene-specific methylation was also assessed in the imprinted lociH19 (non-protein coding RNA transcript promoter andH19 ICR, differentially methylated domain) andKCNQ1 (potassium voltage-gated channel, KQT-like subfamily, member 1) and the non-imprinted glucocorticoid receptor gene (GCR). The degree of methylation was expressed as the percentage of methylated cytosines divided by the sum of methylated and unmethylated cytosines (%5mC). Arsenic, lead, and manganese blood concentrations were measured using inductively-coupled plasma mass spectrometry. Results: Mean (± SD) blood concentrations (microg/dL) of arsenic, lead, and manganese, respectively, were: 1.8 (1.2), 0.8 (0.5), 2.4 (1.2). Arsenic was associated with hypomethylation inH19 (p=0.02) while lead was associated with global hypomethylation measured byline-1 (p=0.02) and also hypomethylation inGCR AllBeta (p=0.04). Manganese was associated with hypomethylation inGCR NR3C1 (p=0.05) and hypermethylation inKCNQ1 (p=0.06) Conclusions: The associations between metals exposure during pregnancy and epigenetic alterations in both imprinted and nonimprinted loci may have implications for the biological mechanisms of action and also suggests that changes in DNA methylation may represent an important biomarker of early biologic effects.
机译:背景:证据表明,金属可能影响表观遗传现象,例如调节基因表达的DNA甲基化。早期生活暴露可能会影响后期疾病的进展,因此,怀孕是研究这些关系的重要时期。目的:评估居住在美国俄克拉荷马州塔克里克超级基金所在地附近的妇女在怀孕期间的DNA甲基化和暴露于多种金属的情况。方法:我们使用PCR-Pyrosequencing〜®定量分析了167名妇女外周血白细胞中亚硫酸氢盐处理的DNA中Alu和LINE-1重复元件的整体甲基化。还评估了印迹的lociH19(非蛋白质编码RNA转录启动子和H19 ICR,差异甲基化域)和KCNQ1(钾电压门控通道,KQT样亚家族,成员1)和非印迹糖皮质激素受体基因中的基因特异性甲基化(GCR)。甲基化程度表示为甲基化胞嘧啶的百分比除以甲基化和未甲基化胞嘧啶的总和(%5mC)。砷,铅和锰的血液浓度使用电感耦合等离子体质谱法进行测量。结果:砷,铅和锰的平均(±SD)血液浓度(microg / dL)分别为:1.8(1.2),0.8(0.5),2.4(1.2)。砷与H19中的甲基化不足有关(p = 0.02),而铅与lineline-1测得的总体甲基化不足(p = 0.02)以及GCR AllBeta中的甲基化不足有关(p = 0.04)。锰与GCR NR3C1中的低甲基化有关(p = 0.05)和KCNQ1中的甲基化过高(p = 0.06)结论:怀孕期间金属暴露与印迹和非印迹基因座的表观遗传改变之间的关联可能对生物学作用机制有影响,并且还暗示DNA甲基化的变化可能代表了早期生物学效应的重要生物标志。

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