House John S, Hall Jonathan, Park Sarah S, Planchart Antonio, Money Eric, Maguire Rachel L, Huang Zhiqing, Mattingly Carolyn J, Skaar David, Tzeng Jung Ying, Darrah Thomas H, Vengosh Avner, Murphy Susan K, Jirtle Randy L, Hoyo Cathrine
Center for Human Health and the Environment, North Carolina State University, Raleigh, NC, USA.
Bioinformatics Research Center, North Carolina State University, Raleigh, NC, USA.
Environ Epigenet. 2019 Aug 29;5(3):dvz014. doi: 10.1093/eep/dvz014. eCollection 2019 Jul.
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 gene that regulates the expression of a cluster of genes including and 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 . Correlations were used to examine potential sources and routes. We observed a significant geographic co-clustering of elevated prenatal Cd levels and DMR hypermethylation in cord blood ( = 0.01), and these findings were substantiated in our statistical models (β = 1.70, se = 0.80, = 0.03). These associations were strongest in those born to African American women (β = 3.52, se = 1.32, = 0.01) compared with those born to White women (β = 1.24, se = 2.11, = 0.56) or Hispanic women (β = 1.18, se = 1.24, = 0.34). Consistent with Cd bioaccumulation during the life course, blood Cd levels increased with age (β = 0.015 µg/dl/year, = 0.003), and Cd concentrations were significantly correlated between blood and urine (ρ > 0.47, < 0.01), but not hand wipe, soil or house dust concentrations ( > 0.05). Together, these data support that prenatal Cd exposure is associated with aberrant methylation of the imprint regulatory element for the 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.
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问题相关。然而，隐匿的暴露源常常阻碍预防工作。此外，尽管怀疑表观遗传机制将这些关联联系起来，但镉靶向的基因序列区域尚不清楚。调节包括 和 在内的一组基因表达的基因上一个差异甲基化区域（DMR）的异常甲基化与多种癌症有关。在287对母婴中，我们结合线性回归和Getis-Ord Gi*统计量来确定母亲血液中的镉浓度是否与后代中调节包括 在内的一组印记基因序列区域的CpG甲基化有关。使用相关性分析来研究潜在的来源和途径。我们观察到产前镉水平升高与脐带血中DMR高甲基化在地理上存在显著的共聚集（ = 0.01），并且这些发现在我们的统计模型中得到了证实（β = 1.70，标准误 = 0.80， = 0.03）。与白人女性所生孩子（β = 1.24，标准误 = 2.11， = 0.56）或西班牙裔女性所生孩子（β = 1.18，标准误 = 1.24， = 0.34）相比，这些关联在非裔美国女性所生孩子中最为强烈（β = 3.52，标准误 = 1.32， = 0.01）。与生命过程中镉的生物累积一致，血液中的镉水平随年龄增长而升高（β = 0.015 μg/dl/年， = 0.003），并且血液和尿液中的镉浓度显著相关（ρ > 0.47， < 0.01），但与手部擦拭物、土壤或室内灰尘浓度无关（ > 0.05）。总之，这些数据支持产前镉暴露与出生时 基因簇印记调控元件的异常甲基化有关。然而，家庭灰尘和水都不太可能是暴露源，并且通过受污染的手摄入也不太可能是该人群的主要暴露途径。需要进行更大规模的研究来确定暴露途径和来源。
