Arsenic Exposure, Blood DNA Methylation, and Cardiovascular Disease.

MedStar author(s):
Citation: Circulation Research. :101161CIRCRESAHA122320991, 2022 Jun 06PMID: 35658476Institution: MedStar Health Research InstituteForm of publication: Journal ArticleMedline article type(s): Journal ArticleSubject headings: IN PROCESS -- NOT YET INDEXEDYear: 2022Local holdings: Available online from MWHC library: 1953 - presentISSN:
  • 0009-7330
Name of journal: Circulation researchAbstract: BACKGROUND: Epigenetic dysregulation has been proposed as a key mechanism for arsenic-related cardiovascular disease (CVD). We evaluated differentially methylated positions (DMPs) as potential mediators on the association between arsenic and CVD.CONCLUSIONS: Differential DNA methylation might be part of the biological link between arsenic and CVD. The gene functions suggest that diabetes might represent a relevant mechanism for arsenic-related cardiovascular risk in populations with a high burden of diabetes.METHODS: Blood DNA methylation was measured in 2321 participants (mean age 56.2, 58.6% women) of the Strong Heart Study, a prospective cohort of American Indians. Urinary arsenic species were measured using high-performance liquid chromatography coupled to inductively coupled plasma mass spectrometry. We identified DMPs that are potential mediators between arsenic and CVD. In a cross-species analysis, we compared those DMPs with differential liver DNA methylation following early-life arsenic exposure in the apoE knockout (apoE-/-) mouse model of atherosclerosis.RESULTS: A total of 20 and 13 DMPs were potential mediators for CVD incidence and mortality, respectively, several of them annotated to genes related to diabetes. Eleven of these DMPs were similarly associated with incident CVD in 3 diverse prospective cohorts (Framingham Heart Study, Women's Health Initiative, and Multi-Ethnic Study of Atherosclerosis). In the mouse model, differentially methylated regions in 20 of those genes and DMPs in 10 genes were associated with arsenic.All authors: Best LG, Bozack AK, Cole SA, Craig Johnson W, Daniele Fallin M, Domingo-Relloso A, Durda P, Galvez-Fernandez M, Glabonjat RA, Goessler W, Haack K, Herreros-Martinez M, Howard BV, Joehanes R, Kasela S, Kent JW Jr, Klein KO, Lappalainen T, Levy D, Liu Y, Lohman K, Makhani K, Mann KK, Moon KA, Navas-Acien A, Rich SS, Riffo-Campos AL, Rotter JI, Sanchez TR, Schilling K, Subedi P, Taylor KD, Tellez-Plaza M, Tracy RP, Umans JG, Van Den Berg D, Vasan RS, Zhang Y, Zhao JFiscal year: FY2022Digital Object Identifier: ORCID: Date added to catalog: 2022-07-06
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Item type Current library Collection Call number Status Date due Barcode
Journal Article MedStar Authors Catalog Article 35658476 Available 35658476

Available online from MWHC library: 1953 - present

BACKGROUND: Epigenetic dysregulation has been proposed as a key mechanism for arsenic-related cardiovascular disease (CVD). We evaluated differentially methylated positions (DMPs) as potential mediators on the association between arsenic and CVD.

CONCLUSIONS: Differential DNA methylation might be part of the biological link between arsenic and CVD. The gene functions suggest that diabetes might represent a relevant mechanism for arsenic-related cardiovascular risk in populations with a high burden of diabetes.

METHODS: Blood DNA methylation was measured in 2321 participants (mean age 56.2, 58.6% women) of the Strong Heart Study, a prospective cohort of American Indians. Urinary arsenic species were measured using high-performance liquid chromatography coupled to inductively coupled plasma mass spectrometry. We identified DMPs that are potential mediators between arsenic and CVD. In a cross-species analysis, we compared those DMPs with differential liver DNA methylation following early-life arsenic exposure in the apoE knockout (apoE-/-) mouse model of atherosclerosis.

RESULTS: A total of 20 and 13 DMPs were potential mediators for CVD incidence and mortality, respectively, several of them annotated to genes related to diabetes. Eleven of these DMPs were similarly associated with incident CVD in 3 diverse prospective cohorts (Framingham Heart Study, Women's Health Initiative, and Multi-Ethnic Study of Atherosclerosis). In the mouse model, differentially methylated regions in 20 of those genes and DMPs in 10 genes were associated with arsenic.

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