Genetic Susceptibility to Cardiovascular Effects of Arsenic Exposure Project summary cardiovascular disease (CVD) is the leading cause of death worldwide. Recent experimental studies support the hypothesis that As exposure leads to oxidative stress and vascular inflammation, a central mechanism to the development of atherosclerosis and CVD. Studies of other health effects of As exposure have suggested effect-modification by As methylation capacity and genetic susceptibility. However, epidemiologic studies of genetic susceptibility to the effects of As exposure on CVD risk are lacking. In the year 2000, we established the Health Effects of Arsenic Longitudinal Study (HEALS), a prospective cohort study of 11,746 participants (original cohort), in Araihazar, Bangladesh. In 2007, HEALS recruited another 8,288 participants (expansion cohort) to include a total of 20,034 participants. More than 90% of the cohort have exposed to As exposure at low-to-moderate levels (<300 5g/L), providing us with a unique opportunity to assess health effects of As exposure from drinking water at the levels of public health interest. As part of the parent study, cardiovascular outcomes of the cohort participants are being ascertained, and carotid artery intima-medial thickness (IMT) is being measured for 1,160 participants randomly selected from the original cohort. On the basis of these resources, our substantial pilot data, as well as cohort analyses which show a positive association between As exposure and CVD incidence and mortality, we propose a series of analyses to assess the genetic susceptibility to the effects of As exposure on the risk of atherosclerosis and CVD. We will evaluate whether the cardiovascular effects of As exposure differ by polymorphisms in genes related to As methylation (GSTM1, GSTT1, GSTO1, GSTP1, MTHFR, and AS3MT genes) and genes related to oxidative stress (NOS3, SOD2, and CYBA) and inflammation/endothelial dysfunction (TNF, IL6, ICAM1, and VCAM1) using a cross-sectional study of IMT with the subcohort of 1,160 participants, and a case-cohort study of CVD risk with 692 cases and the same subcohort of 1,160 participants from the original cohort. The strongest gene- As interaction will be tested again in a second case-cohort study with 305 cases and another subcohort of 520 participants selected from the expansion cohort. To further characterize the underlying mechanisms by which As exposure causes CVD, we will conduct a cross-sectional study with 300 subjects to evaluate the associations between As exposure and serum/urinary phenotypic markers for oxidative stress and inflammation. The proposed study will provide valuable knowledge about the pathophysiology and mechanism by which As exposure may lead to CVD and may also lead to improved prevention and risk assessment of As exposure.

Public Health Relevance

The proposed project aims to assess whether low-to-moderate level of inorganic arsenic from drinking water increases the risk of cardiovascular disease in genetic susceptible groups to oxidative stress, inflammation, and low As metabolism capacity. The proposed study will contribute to the knowledge about the pathophysiology and mechanism by which arsenic exposure may lead to cardiovascular diseases. The findings may also improve risk assessment of health effects of arsenic exposure.

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Research Project (R01)
Project #
5R01ES017541-05
Application #
8502262
Study Section
Special Emphasis Panel (ZES1-JAB-G (R3))
Program Officer
Mcallister, Kimberly A
Project Start
2009-09-11
Project End
2014-06-30
Budget Start
2013-07-01
Budget End
2014-06-30
Support Year
5
Fiscal Year
2013
Total Cost
$412,348
Indirect Cost
$85,423
Name
New York University
Department
Public Health & Prev Medicine
Type
Schools of Medicine
DUNS #
121911077
City
New York
State
NY
Country
United States
Zip Code
10016
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Wu, Fen; Chen, Yu; Demmer, Ryan T et al. (2016) Periodontal diseases and carotid intima-media thickness in Bangladesh. J Clin Periodontol 43:909-917
Farzan, Shohreh F; Gossai, Anala; Chen, Yu et al. (2016) Maternal arsenic exposure and gestational diabetes and glucose intolerance in the New Hampshire birth cohort study. Environ Health 15:106
Farzan, Shohreh F; Chen, Yu; Trachtman, Howard et al. (2016) Urinary polycyclic aromatic hydrocarbons and measures of oxidative stress, inflammation and renal function in adolescents: NHANES 2003-2008. Environ Res 144:149-57
Farzan, Shohreh F; Karagas, Margaret R; Jiang, Jieying et al. (2015) Gene-arsenic interaction in longitudinal changes of blood pressure: Findings from the Health Effects of Arsenic Longitudinal Study (HEALS) in Bangladesh. Toxicol Appl Pharmacol 288:95-105
Jiang, Jieying; Liu, Mengling; Parvez, Faruque et al. (2015) Association between Arsenic Exposure from Drinking Water and Longitudinal Change in Blood Pressure among HEALS Cohort Participants. Environ Health Perspect 123:806-12
Wu, Fen; Jasmine, Farzana; Kibriya, Muhammad G et al. (2015) Interaction between arsenic exposure from drinking water and genetic polymorphisms on cardiovascular disease in Bangladesh: a prospective case-cohort study. Environ Health Perspect 123:451-7
Jiang, Jieying; Liu, Mengling; Parvez, Faruque et al. (2015) Association of major dietary patterns and blood pressure longitudinal change in Bangladesh. J Hypertens 33:1193-200
Farzan, Shohreh F; Chen, Yu; Rees, Judy R et al. (2015) Risk of death from cardiovascular disease associated with low-level arsenic exposure among long-term smokers in a US population-based study. Toxicol Appl Pharmacol 287:93-7
Farzan, Shohreh F; Chen, Yu; Wu, Fen et al. (2015) Blood Pressure Changes in Relation to Arsenic Exposure in a U.S. Pregnancy Cohort. Environ Health Perspect 123:999-1006

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