Cadmium exposure and MEG3 methylation differences between Whites and African Americans in the NEST Cohort

John S. House, Jonathan Hall, Sarah S. Park, Antonio Planchart, Eric Money, Rachel L. Maguire, Zhiqing Huang, Carolyn J. Mattingly, David Skaar, Jung Ying Tzeng, Thomas H. Darrah, Avner Vengosh, Susan K. Murphy, Randy L. Jirtle, Cathrine Hoyo

研究成果: Article同行評審

6 引文 斯高帕斯(Scopus)

摘要

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 < 0.01), but not hand wipe, soil or house dust concentrations (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.

原文English
文章編號dvz014
期刊Environmental Epigenetics
5
發行號3
DOIs
出版狀態Published - 2019 7月 1

All Science Journal Classification (ASJC) codes

  • 遺傳學
  • 分子生物學
  • 健康、毒理學和誘變
  • 遺傳學(臨床)

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