Arsenic Exposure, Blood DNA Methylation, and Cardiovascular Disease,Circulation Research

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Arsenic Exposure, Blood DNA Methylation, and Cardiovascular Disease
Circulation Research ( IF 20.1 ) Pub Date : 2022-06-06 , DOI: 10.1161/circresaha.122.320991
Arce Domingo-Relloso _{1,

2,

3} , Kiran Makhani ₄ , Angela L Riffo-Campos _{5,

6} , Maria Tellez-Plaza ₂ , Kathleen Oros Klein ₄ , Pooja Subedi ₇ , Jinying Zhao ₇ , Katherine A Moon ₈ , Anne K Bozack ₉ , Karin Haack ₁₀ , Walter Goessler ₁₁ , Jason G Umans _{12,

13} , Lyle G Best ₁₄ , Ying Zhang ₁₅ , Miguel Herreros-Martinez ₁₆ , Ronald A Glabonjat ₁ , Kathrin Schilling ₁ , Marta Galvez-Fernandez _{1,

2} , Jack W Kent ₁₀ , Tiffany R Sanchez ₁ , Kent D Taylor ₁₇ , W Craig Johnson ₁₈ , Peter Durda ₁₉ , Russell P Tracy ₁₉ , Jerome I Rotter ₁₇ , Stephen S Rich ₂₀ , David Van Den Berg ₂₁ , Silva Kasela _{22,

23} , Tuuli Lappalainen _{22,

23} , Ramachandran S Vasan _{24,

25} , Roby Joehanes _{26,

27} , Barbara V Howard _{12,

13} , Daniel Levy _{26,

27} , Kurt Lohman ₂₈ , Yongmei Liu ₂₈ , M Daniele Fallin ₂₉ , Shelley A Cole ₁₀ , Koren K Mann _{4,

30} , Ana Navas-Acien ₁

Affiliation

Department of Environmental Health Sciences, Columbia University Mailman School of Public Health, New York, NY (A.D.-R., R.A.G., K.S., M.G.-F., T.R.S., A.N.-A.).
Integrative Epidemiology Group, Department of Chronic Diseases Epidemiology, National Center for Epidemiology, Carlos III Health Institute, Madrid, Spain (A.D.-R., M.T.-P., M.G.-F.).
Department of Statistics and Operations Research (A.D.-R.), University of Valencia, Spain.
Lady Davis Institute for Medical Research, Jewish General Hospital, Montreal, Quebec, Canada (K.M., K.O.K., K.K.M.).
Department of Computer Science, ETSE (A.L.R.-C.), University of Valencia, Spain.
Millennium Nucleus on Sociomedicine (SocioMed) and Vicerrectoría Académica, Universidad de La Frontera, Temuco, Chile (A.L.R.-C.).
Department of Epidemiology, College of Public Health and Health Professions and College of Medicine, University of Florida, Gainesville (P.S., J.Z.).
Department of Environmental Health and Engineering, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD (K.A.M.).
Department of Environmental Health Sciences, School of Public Health, University of California, Berkeley (A.K.B.).
Population Health Program, Texas Biomedical Research Institute, San Antonio' TX (K.H., J.W.K., S.A.C.).
Institute of Chemistry - Analytical Chemistry for Health and Environment, University of Graz, Austria (W.G.).
MedStar Health Research Institute, Hyattsville, MD. Now with Georgetown-Howard Universities Center for Clinical and Translational Science, Washington, DC (J.G.U., B.W.H.).
Georgetown-Howard Universities Center for Clinical and Translational Science, Washington, DC (J.G.U., B.V.H.).
Missouri Breaks Industries and Research, Inc, Eagle Butte, SD (L.G.B.).
Department of Biostatistics and Epidemiology, The University of Oklahoma Health Sciences Center (Y.Z.).
Bioinformatics Unit, Institute for Biomedical Research INCLIVA, Valencia, Spain (M.H.-M.).
The Institute for Translational Genomics and Population Sciences, Department of Pediatrics, The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, CA (K.D.T., J.I.R.).
Department of Biostatistics, University of Washington, Seattle (W.C.J.).
Department of Pathology Laboratory Medicine, Larner College of Medicine, University of Vermont, Burlington, VT (P.D., R.P.T.).
Center for Public Health Genomics, Department of Public Health Sciences, University of Virginia, Charlottesville, VA (S.S.R.).
Department of Population and Public Health Sciences, Keck School of Medicine of USC, University of Southern California, Los Angeles' CA (D.V.D.B.).
New York Genome Center (S.K., T.L.).
Department of Systems Biology, Columbia University' NY (S.K., T.L.).
National Heart, Lung, and Blood Institute's and Boston University's Framingham Heart Study, Framingham, MA (R.S.V.).
Sections of Preventive Medicine and Epidemiology and Cardiovascular Medicine, Department of Medicine, Department of Epidemiology, Boston University Schools of Medicine and Public Health, MA (R.S.V.).
Population Sciences Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD (R.J., D.L.).
Framingham Heart Study, MA (R.J., D.L.).
Department of Medicine, Duke University Medical Center, Durham, NC (K.L., Y.L.).
Departments of Mental Health and Epidemiology, Johns Hopkins University, Baltimore, MD (M.D.F.).
Department of Pharmacology and Therapeutics, McGill University, Montreal, Canada (K.K.M.).

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.

中文翻译：

砷暴露、血液 DNA 甲基化和心血管疾病

背景：表观遗传失调已被认为是砷相关心血管疾病（CVD）的关键机制。我们评估了差异甲基化位置 (DMP) 作为砷与 CVD 之间关联的潜在调节因素。方法：对强心脏研究（美国印第安人前瞻性队列）的 2321 名参与者（平均年龄 56.2 岁，58.6% 女性）进行了血液 DNA 甲基化测量。使用高效液相色谱与电感耦合等离子体质谱联用测量尿砷形态。我们发现 DMP 是砷和 CVD 之间的潜在中介。在跨物种分析中，我们比较了 apoE 敲除（apoE ^−/−）动脉粥样硬化小鼠模型。结果：共有 20 种和 13 种 DMP 分别是 CVD 发病率和死亡率的潜在介质，其中几种注释为与糖尿病相关的基因。在 3 个不同的前瞻性队列（弗雷明汉心脏研究、妇女健康倡议和动脉粥样硬化多种族研究）中，其中 11 个 DMP 与 CVD 事件相似。在小鼠模型中，其中20个基因的差异甲基化区域和10个基因的DMP与砷相关。结论：差异DNA甲基化可能是砷与CVD之间生物学联系的一部分。基因功能表明，糖尿病可能代表糖尿病高负担人群中砷相关心血管风险的相关机制。

更新日期：2022-06-06

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