Arsenic Exposure, Blood DNA Methylation, and Cardiovascular Disease

Arce Domingo-Relloso; Kiran Makhani; Angela L. Riffo-Campos; Maria Tellez-Plaza; Kathleen Oros Klein; Pooja Subedi; Jinying Zhao; Katherine A. Moon; Anne K. Bozack; Karin Haack; Walter Goessler; Jason G. Umans; Lyle G. Best; Ying Zhang; Miguel Herreros-Martinez; Ronald A. Glabonjat; Kathrin Schilling; Marta Galvez-Fernandez; Jack W. Kent; Tiffany R. Sanchez; Kent D. Taylor; W. Craig Johnson; Peter Durda; Russell P. Tracy; Jerome I. Rotter; Stephen S. Rich; David Van Den Berg; Silva Kasela; Tuuli Lappalainen; Ramachandran S. Vasan; Roby Joehanes; Barbara V. Howard; Daniel Levy; Kurt Lohman; Yongmei Liu; M. Daniele Fallin; Shelley A. Cole; Koren K. Mann; Ana Navas-Acien

doi:10.1161/CIRCRESAHA.122.320991

Arsenic Exposure, Blood DNA Methylation, and Cardiovascular Disease

Arce Domingo-Relloso, Kiran Makhani, Angela L. Riffo-Campos, Maria Tellez-Plaza, Kathleen Oros Klein, Pooja Subedi, Jinying Zhao, Katherine A. Moon, Anne K. Bozack, Karin Haack, Walter Goessler, Jason G. Umans, Lyle G. Best, Ying Zhang, Miguel Herreros-Martinez, Ronald A. Glabonjat, Kathrin Schilling, Marta Galvez-Fernandez, Jack W. Kent, Tiffany R. SanchezKent D. Taylor, W. Craig Johnson, Peter Durda, Russell P. Tracy, Jerome I. Rotter, Stephen S. Rich, David Van Den Berg, Silva Kasela, Tuuli Lappalainen, Ramachandran S. Vasan, Roby Joehanes, Barbara V. Howard, Daniel Levy, Kurt Lohman, Yongmei Liu, M. Daniele Fallin, Shelley A. Cole, Koren K. Mann, Ana Navas-Acien

Research output: Contribution to journal › Article › peer-review

37 Scopus citations

Abstract

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. 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. 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.

Original language	English (US)
Pages (from-to)	E51-E69
Journal	Circulation research
Volume	131
Issue number	2
DOIs	https://doi.org/10.1161/CIRCRESAHA.122.320991
State	Published - Jul 8 2022
Externally published	Yes

Keywords

DNA methylation
arsenic
cardiovascular diseases

ASJC Scopus subject areas

Physiology
Cardiology and Cardiovascular Medicine

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10.1161/CIRCRESAHA.122.320991

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Domingo-Relloso, A., Makhani, K., Riffo-Campos, A. L., Tellez-Plaza, M., Klein, K. O., Subedi, P., Zhao, J., Moon, K. A., Bozack, A. K., Haack, K., Goessler, W., Umans, J. G., Best, L. G., Zhang, Y., Herreros-Martinez, M., Glabonjat, R. A., Schilling, K., Galvez-Fernandez, M., Kent, J. W., ... Navas-Acien, A. (2022). Arsenic Exposure, Blood DNA Methylation, and Cardiovascular Disease. Circulation research, 131(2), E51-E69. https://doi.org/10.1161/CIRCRESAHA.122.320991

Domingo-Relloso, A, Makhani, K, Riffo-Campos, AL, Tellez-Plaza, M, Klein, KO, Subedi, P, Zhao, J, Moon, KA, Bozack, AK, Haack, K, Goessler, W, Umans, JG, Best, LG, Zhang, Y, Herreros-Martinez, M, Glabonjat, RA, Schilling, K, Galvez-Fernandez, M, Kent, JW, Sanchez, TR, Taylor, KD, Johnson, WC, Durda, P, Tracy, RP, Rotter, JI, Rich, SS, Van Den Berg, D, Kasela, S, Lappalainen, T, Vasan, RS, Joehanes, R, Howard, BV, Levy, D, Lohman, K, Liu, Y, Fallin, MD, Cole, SA, Mann, KK & Navas-Acien, A 2022, 'Arsenic Exposure, Blood DNA Methylation, and Cardiovascular Disease', Circulation research, vol. 131, no. 2, pp. E51-E69. https://doi.org/10.1161/CIRCRESAHA.122.320991

@article{5fe7d95314e44c14ab7bf7a856f8e6f9,

title = "Arsenic Exposure, Blood DNA Methylation, and Cardiovascular Disease",

abstract = "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. 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. 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.",

keywords = "DNA methylation, arsenic, cardiovascular diseases",

author = "Arce Domingo-Relloso and Kiran Makhani and Riffo-Campos, {Angela L.} and Maria Tellez-Plaza and Klein, {Kathleen Oros} and Pooja Subedi and Jinying Zhao and Moon, {Katherine A.} and Bozack, {Anne K.} and Karin Haack and Walter Goessler and Umans, {Jason G.} and Best, {Lyle G.} and Ying Zhang and Miguel Herreros-Martinez and Glabonjat, {Ronald A.} and Kathrin Schilling and Marta Galvez-Fernandez and Kent, {Jack W.} and Sanchez, {Tiffany R.} and Taylor, {Kent D.} and Johnson, {W. Craig} and Peter Durda and Tracy, {Russell P.} and Rotter, {Jerome I.} and Rich, {Stephen S.} and {Van Den Berg}, David and Silva Kasela and Tuuli Lappalainen and Vasan, {Ramachandran S.} and Roby Joehanes and Howard, {Barbara V.} and Daniel Levy and Kurt Lohman and Yongmei Liu and Fallin, {M. Daniele} and Cole, {Shelley A.} and Mann, {Koren K.} and Ana Navas-Acien",

year = "2022",

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doi = "10.1161/CIRCRESAHA.122.320991",

language = "English (US)",

volume = "131",

pages = "E51--E69",

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publisher = "Lippincott Williams and Wilkins",

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TY - JOUR

T1 - Arsenic Exposure, Blood DNA Methylation, and Cardiovascular Disease

AU - Domingo-Relloso, Arce

AU - Makhani, Kiran

AU - Riffo-Campos, Angela L.

AU - Tellez-Plaza, Maria

AU - Klein, Kathleen Oros

AU - Subedi, Pooja

AU - Zhao, Jinying

AU - Moon, Katherine A.

AU - Bozack, Anne K.

AU - Haack, Karin

AU - Goessler, Walter

AU - Umans, Jason G.

AU - Best, Lyle G.

AU - Zhang, Ying

AU - Herreros-Martinez, Miguel

AU - Glabonjat, Ronald A.

AU - Schilling, Kathrin

AU - Galvez-Fernandez, Marta

AU - Kent, Jack W.

AU - Sanchez, Tiffany R.

AU - Taylor, Kent D.

AU - Johnson, W. Craig

AU - Durda, Peter

AU - Tracy, Russell P.

AU - Rotter, Jerome I.

AU - Rich, Stephen S.

AU - Van Den Berg, David

AU - Kasela, Silva

AU - Lappalainen, Tuuli

AU - Vasan, Ramachandran S.

AU - Joehanes, Roby

AU - Howard, Barbara V.

AU - Levy, Daniel

AU - Lohman, Kurt

AU - Liu, Yongmei

AU - Fallin, M. Daniele

AU - Cole, Shelley A.

AU - Mann, Koren K.

AU - Navas-Acien, Ana

PY - 2022/7/8

Y1 - 2022/7/8

N2 - 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. 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. 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.

AB - 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. 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. 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.

KW - DNA methylation

KW - arsenic

KW - cardiovascular diseases

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U2 - 10.1161/CIRCRESAHA.122.320991

DO - 10.1161/CIRCRESAHA.122.320991

M3 - Article

C2 - 35658476

AN - SCOPUS:85134321203

SN - 0009-7330

VL - 131

SP - E51-E69

JO - Circulation research

JF - Circulation research

IS - 2

ER -

Arsenic Exposure, Blood DNA Methylation, and Cardiovascular Disease

Abstract

Keywords

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