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首页> 外文期刊>Environmental Epigenetics >Cadmium exposure and MEG3 methylation differences between Whites and African Americans in the NEST Cohort
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Cadmium exposure and MEG3 methylation differences between Whites and African Americans in the NEST Cohort

机译：NEST队列中白人与非裔美国人之间的镉暴露和MEG3甲基化差异

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Cadmium (Cd) is a ubiquitous environmental pollutant associated with a wide range of health outcomes including cancer. However, obscure exposure sources often hinder prevention efforts. Further, although epigenetic mechanisms are suspected to link these associations, gene sequence regions targeted by Cd are unclear. Aberrant methylation of a differentially methylated region (DMR) on the MEG3 gene that regulates the expression of a cluster of genes including MEG3, DLK1, MEG8, MEG9 and DIO3 has been associated with multiple cancers. In 287 infant–mother pairs, we used a combination of linear regression and the Getis-Ord Gi* statistic to determine if maternal blood Cd concentrations were associated with offspring CpG methylation of the sequence region regulating a cluster of imprinted genes including MEG3 . Correlations were used to examine potential sources and routes. We observed a significant geographic co-clustering of elevated prenatal Cd levels and MEG3 DMR hypermethylation in cord blood ( P =?0.01), and these findings were substantiated in our statistical models (β?=?1.70, se?=?0.80, P =?0.03). These associations were strongest in those born to African American women (β?=?3.52, se?=?1.32, P =?0.01) compared with those born to White women (β?=?1.24, se?=?2.11, P =?0.56) or Hispanic women (β?=?1.18, se?=?1.24, P =?0.34). Consistent with Cd bioaccumulation during the life course, blood Cd levels increased with age (β?=?0.015?μg/dl/year, P =?0.003), and Cd concentrations were significantly correlated between blood and urine (ρ??0.47, P ?0.05). Together, these data support that prenatal Cd exposure is associated with aberrant methylation of the imprint regulatory element for the MEG3 gene cluster at birth. However, neither house-dust nor water are likely exposure sources, and ingestion via contaminated hands is also unlikely to be a significant exposure route in this population. Larger studies are required to identify routes and sources of exposure.
机译：镉（Cd）是一种普遍存在的环境污染物，与包括癌症在内的多种健康后果有关。但是，模糊的暴露源通常会阻碍预防工作。此外，尽管怀疑是表观遗传机制将这些关联联系起来，但Cd靶向的基因序列区域尚不清楚。调节包括MEG3，DLK1，MEG8，MEG9和DIO3在内的基因簇表达的MEG3基因上的甲基化差异区域（DMR）异常甲基化与多种癌症有关。在287对母婴对中，我们使用线性回归和Getis-Ord Gi *统计量的组合来确定母体血液Cd浓度是否与调节包括MEG3在内的印记基因簇的序列区域的后代CpG甲基化相关。相关性用于检查潜在的来源和路线。我们观察到脐血中升高的产前Cd水平和MEG3 DMR甲基化水平显着地在地理上成簇（P =？0.01），这些发现在我们的统计模型中得到了证实（β？=？1.70，se？=？0.80，P =？0.03）。与白人妇女（β≥1.24，se≥2.11，P≥0.01）相比，这些关联在非裔美国女性所生（β≥3.52，se≥1.32，P = 0.01）中最强。 =？0.56）或西班牙裔女性（β？=？1.18，se？=？1.24，P =？0.34）。在生活过程中，与镉的生物蓄积一致，血液中的镉水平随着年龄的增长而增加（β≥0.015μg/ dl /年，P = 0.003），血液和尿液中镉的浓度显着相关（ρ≥0.47）。 ，P ＜0.05）。总之，这些数据支持出生前Cd暴露与出生时MEG3基因簇的印迹调节元件的异常甲基化有关。但是，无论是房屋灰尘还是水都不可能成为暴露源，通过受污染的手摄入也不大可能是该人群的主要暴露途径。需要更大的研究来确定暴露的途径和来源。

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