Genetic Susceptibilty to Cardiovascular Effects of Arsenic Exposure

Summary

Principal Investigator: Yu Chen
Abstract: DESCRIPTION (provided by applicant): 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.
Funding Period: 2009-09-11 - 2014-06-30
more information: NIH RePORT

Top Publications

  1. pmc Association between arsenic exposure from drinking water and proteinuria: results from the Health Effects of Arsenic Longitudinal Study
    Yu Chen
    Department of Environmental Medicine, New York University School of Medicine, New York, NY, USA
    Int J Epidemiol 40:828-35. 2011
  2. pmc Association between arsenic exposure from drinking water and hematuria: results from the Health Effects of Arsenic Longitudinal Study
    Tyler R McClintock
    Department of Population Health, New York University School of Medicine, New York, NY, USA Department of Environmental Medicine, New York University School of Medicine, New York, NY, USA Department of Urology, New York University School of Medicine, New York, NY, USA
    Toxicol Appl Pharmacol 276:21-7. 2014
  3. pmc Association between anthropometric measures of obesity and subclinical atherosclerosis in Bangladesh
    Wenzhen Ge
    Department of Environmental Medicine, New York University School of Medicine, New York, NY, USA
    Atherosclerosis 232:234-41. 2014
  4. pmc In utero and early life arsenic exposure in relation to long-term health and disease
    Shohreh F Farzan
    Children s Environmental Health and Disease Prevention Research Center at Dartmouth, Hanover, NH 03755, USA Section of Biostatistics and Epidemiology, Department of Community and Family Medicine and Norris Cotton Cancer Center, Geisel School of Medicine at Dartmouth, Lebanon, NH 03756, USA
    Toxicol Appl Pharmacol 272:384-90. 2013
  5. pmc Arsenic exposure from drinking water, arsenic methylation capacity, and carotid intima-media thickness in Bangladesh
    Yu Chen
    Departments of Population Health and Environmental Medicine, School of Medicine, New York University, 650 First Avenue, Room 510, New York, NY 10016, USA
    Am J Epidemiol 178:372-81. 2013
  6. pmc A prospective study of arsenic exposure, arsenic methylation capacity, and risk of cardiovascular disease in Bangladesh
    Yu Chen
    Department of Population Health, New York University School of Medicine, New York, New York 10016, USA
    Environ Health Perspect 121:832-8. 2013
  7. pmc A prospective study of tobacco smoking and mortality in Bangladesh
    Fen Wu
    Department of Population Health, New York University School of Medicine, New York, New York, United States of America
    PLoS ONE 8:e58516. 2013
  8. pmc Arsenic exposure from drinking water and QT-interval prolongation: results from the Health Effects of Arsenic Longitudinal Study
    Yu Chen
    Department of Population Health, New York University School of Medicine, New York University, New York, New York 10016 USA
    Environ Health Perspect 121:427-32. 2013
  9. pmc Prospective investigation of major dietary patterns and risk of cardiovascular mortality in Bangladesh
    Yu Chen
    Department of Environmental Medicine, New York University School of Medicine, New York, NY, USA
    Int J Cardiol 167:1495-501. 2013
  10. pmc Association between arsenic exposure from drinking water and plasma levels of cardiovascular markers
    Fen Wu
    Department of Environmental Medicine, New York University School of Medicine, New York, USA
    Am J Epidemiol 175:1252-61. 2012

Research Grants

  1. EPIDEMIOLOGY OF ALCOHOL PROBLEMS
    Thomas K Greenfield; Fiscal Year: 2013
  2. Molecular Regulation of Mammalian Meiosis
    Kenneth Paigen; Fiscal Year: 2013
  3. NMR AND COMPUTATIONAL STUDIES OF BIOMOLECULES
    Gerhard Wagner; Fiscal Year: 2013
  4. Comparative Mechanisms of Cancer Chemoprevention
    Roderick H Dashwood; Fiscal Year: 2013
  5. Epidemiological Research on Autism in Jamaica - Phase II
    Mohammad H Rahbar; Fiscal Year: 2013
  6. Is Low-Level Arsenic Exposure Related to Neurobehavioral Deficits in Children
    Katarzyna Kordas; Fiscal Year: 2013
  7. EPIDEMIOLOGY OF AGE-RELATED HEARING LOSS
    Karen J Cruickshanks; Fiscal Year: 2013
  8. Mediators of Atherosclerosis in South Asians Living in America
    Alka M Kanaya; Fiscal Year: 2013
  9. Elucidating Risks: From Exposure and Mechanism to Outcome
    James A Swenberg; Fiscal Year: 2013
  10. Puerto Rico Testsite for Exploring Contamination Threats (PRoTECT)
    Akram N Alshawabkeh; Fiscal Year: 2013

Detail Information

Publications17

  1. pmc Association between arsenic exposure from drinking water and proteinuria: results from the Health Effects of Arsenic Longitudinal Study
    Yu Chen
    Department of Environmental Medicine, New York University School of Medicine, New York, NY, USA
    Int J Epidemiol 40:828-35. 2011
    ..Proteinuria has been recognized as a marker for an increased risk of chronic renal disease. It is unclear whether arsenic (As) exposure from drinking water is associated with proteinuria...
  2. pmc Association between arsenic exposure from drinking water and hematuria: results from the Health Effects of Arsenic Longitudinal Study
    Tyler R McClintock
    Department of Population Health, New York University School of Medicine, New York, NY, USA Department of Environmental Medicine, New York University School of Medicine, New York, NY, USA Department of Urology, New York University School of Medicine, New York, NY, USA
    Toxicol Appl Pharmacol 276:21-7. 2014
    ..17 μg/l, respectively. These data indicate a positive association of As exposure with both prevalence and incidence of dipstick hematuria. This exposure effect appears modifiable by relatively short-term changes in drinking water As...
  3. pmc Association between anthropometric measures of obesity and subclinical atherosclerosis in Bangladesh
    Wenzhen Ge
    Department of Environmental Medicine, New York University School of Medicine, New York, NY, USA
    Atherosclerosis 232:234-41. 2014
    ..However, their relationships with subclinical atherosclerosis are unclear. Studies in normal-weight populations, especially in Asian countries where leanness is prevalent, are lacking...
  4. pmc In utero and early life arsenic exposure in relation to long-term health and disease
    Shohreh F Farzan
    Children s Environmental Health and Disease Prevention Research Center at Dartmouth, Hanover, NH 03755, USA Section of Biostatistics and Epidemiology, Department of Community and Family Medicine and Norris Cotton Cancer Center, Geisel School of Medicine at Dartmouth, Lebanon, NH 03756, USA
    Toxicol Appl Pharmacol 272:384-90. 2013
    ..There is a growing body of evidence that prenatal and early childhood exposure to arsenic from drinking water can have serious long-term health implications...
  5. pmc Arsenic exposure from drinking water, arsenic methylation capacity, and carotid intima-media thickness in Bangladesh
    Yu Chen
    Departments of Population Health and Environmental Medicine, School of Medicine, New York University, 650 First Avenue, Room 510, New York, NY 10016, USA
    Am J Epidemiol 178:372-81. 2013
    ..Future prospective studies are needed to confirm the association between arsenic methylation capacity and atherosclerosis-related outcomes. ..
  6. pmc A prospective study of arsenic exposure, arsenic methylation capacity, and risk of cardiovascular disease in Bangladesh
    Yu Chen
    Department of Population Health, New York University School of Medicine, New York, New York 10016, USA
    Environ Health Perspect 121:832-8. 2013
    ..Few prospective studies have evaluated the influence of arsenic methylation capacity on cardiovascular disease (CVD) risk...
  7. pmc A prospective study of tobacco smoking and mortality in Bangladesh
    Fen Wu
    Department of Population Health, New York University School of Medicine, New York, New York, United States of America
    PLoS ONE 8:e58516. 2013
    ..Limited data are available on smoking-related mortality in low-income countries, where both chronic disease burden and prevalence of smoking are increasing...
  8. pmc Arsenic exposure from drinking water and QT-interval prolongation: results from the Health Effects of Arsenic Longitudinal Study
    Yu Chen
    Department of Population Health, New York University School of Medicine, New York University, New York, New York 10016 USA
    Environ Health Perspect 121:427-32. 2013
    ..Arsenic exposure from drinking water has been associated with heart disease; however, underlying mechanisms are uncertain...
  9. pmc Prospective investigation of major dietary patterns and risk of cardiovascular mortality in Bangladesh
    Yu Chen
    Department of Environmental Medicine, New York University School of Medicine, New York, NY, USA
    Int J Cardiol 167:1495-501. 2013
    ..However, no studies have applied this technique to a population outside of the developed world...
  10. pmc Association between arsenic exposure from drinking water and plasma levels of cardiovascular markers
    Fen Wu
    Department of Environmental Medicine, New York University School of Medicine, New York, USA
    Am J Epidemiol 175:1252-61. 2012
    ....
  11. pmc Betel quid chewing in rural Bangladesh: prevalence, predictors and relationship to blood pressure
    Julia E Heck
    Department of Epidemiology, University of California, Los Angeles, CA, USA
    Int J Epidemiol 41:462-71. 2012
    ..The purpose of our study was to examine the prevalence and predictors of betel quid chewing in a rural area of Bangladesh, and determine its effects on body mass index (BMI) and blood pressure...
  12. pmc Arsenic exposure in Latin America: biomarkers, risk assessments and related health effects
    Tyler R McClintock
    New York University School of Medicine, New York University, New York, NY, USA
    Sci Total Environ 429:76-91. 2012
    ..Targeted future studies will not only yield a better understanding of the public health impact of As in Latin America populations, but also allow for effective and timely mitigation efforts...
  13. pmc Arsenic exposure and toxicology: a historical perspective
    Michael F Hughes
    Office of Research and Development, National Health and Environmental Effects Research Laboratory, U S Environmental Protection Agency, Research Triangle Park, North Carolina 27711, USA
    Toxicol Sci 123:305-32. 2011
    ..With advances in technology and the recent development of animal models for arsenic carcinogenicity, understanding of the toxicology of arsenic will continue to improve...
  14. pmc Inference for causal interactions for continuous exposures under dichotomization
    Tyler J VanderWeele
    Department of Epidemiology, Harvard School of Public Health, 677 Huntington Avenue, Boston, Massachusetts 02115, USA
    Biometrics 67:1414-21. 2011
    ..The results in this article are applied to a study of the interactive effects between smoking and arsenic exposure from well water in producing skin lesions...
  15. pmc Arsenic exposure from drinking water and mortality from cardiovascular disease in Bangladesh: prospective cohort study
    Yu Chen
    Department of Environmental Medicine, New York University School of Medicine, New York, NY 10016, USA
    BMJ 342:d2431. 2011
    ..To evaluate the association between arsenic exposure and mortality from cardiovascular disease and to assess whether cigarette smoking influences the association...
  16. pmc Association between body-mass index and risk of death in more than 1 million Asians
    Wei Zheng
    Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt Ingram Cancer Center, Vanderbilt University, Nashville, TN, USA
    N Engl J Med 364:719-29. 2011
    ..Most studies that have evaluated the association between the body-mass index (BMI) and the risks of death from any cause and from specific causes have been conducted in populations of European origin...
  17. pmc Interaction between arsenic exposure from drinking water and genetic susceptibility in carotid intima-media thickness in Bangladesh
    Fen Wu
    Department of Population Health, New York University School of Medicine, New York, NY, USA Department of Environmental Medicine, New York University School of Medicine, New York, NY, USA
    Toxicol Appl Pharmacol 276:195-203. 2014
    ..Future replication studies in diverse populations are needed to confirm the findings...

Research Grants30

  1. EPIDEMIOLOGY OF ALCOHOL PROBLEMS
    Thomas K Greenfield; Fiscal Year: 2013
    ..We plan to build research capacity in the Center and other organizations, enhance careers of new investigators, and make key findings accessible to researchers, policy makers, practitioners, and the public. ..
  2. Molecular Regulation of Mammalian Meiosis
    Kenneth Paigen; Fiscal Year: 2013
    ..Results of the program project will significantly increase the understanding of the mechanisms that regulate meiosis as well as their involvement in other important biological processes. ..
  3. NMR AND COMPUTATIONAL STUDIES OF BIOMOLECULES
    Gerhard Wagner; Fiscal Year: 2013
    ..We anticipate that the proposed research will continue to advance the capabilities of NMR for structural biology. ..
  4. Comparative Mechanisms of Cancer Chemoprevention
    Roderick H Dashwood; Fiscal Year: 2013
    ..This application is innovative and timely in bridging basic mechanisms, preclinical models, and human studies of epigenetics and diet. ..
  5. Epidemiological Research on Autism in Jamaica - Phase II
    Mohammad H Rahbar; Fiscal Year: 2013
    ....
  6. Is Low-Level Arsenic Exposure Related to Neurobehavioral Deficits in Children
    Katarzyna Kordas; Fiscal Year: 2013
    ....
  7. EPIDEMIOLOGY OF AGE-RELATED HEARING LOSS
    Karen J Cruickshanks; Fiscal Year: 2013
    ..Linking these processes with common conditions of aging could lead to new treatments targeted at reducing the long-term effects of inflammation and atherosclerosis and improve health for tomorrow's elders. ..
  8. Mediators of Atherosclerosis in South Asians Living in America
    Alka M Kanaya; Fiscal Year: 2013
    ..centers to identify risk factors linked to subclinical atherosclerosis and incident cardiovascular disease. These will provide targets for future therapies to prevent or cure the leading cause of death worldwide, cardiovascular disease. ..
  9. Elucidating Risks: From Exposure and Mechanism to Outcome
    James A Swenberg; Fiscal Year: 2013
    ..This Program is highly relevant to Superfund by addressing high-priority chemicals and by focusing on mechanisms underlying health effects, exposure assessment, and remediation to mitigate exposure and toxicity. ..
  10. Puerto Rico Testsite for Exploring Contamination Threats (PRoTECT)
    Akram N Alshawabkeh; Fiscal Year: 2013
    ..The cross-disciplinary approach will employ the data-rich centralized data repository and integrated modeling/analysis capabilities to better understand complex interrelationships between multiple risk factors. ..
  11. Hopkins Center for Eliminate Cardiovascular Health Disparities
    Lisa A Cooper; Fiscal Year: 2013
    ..abstract_text> ..
  12. TOXIC SUBSTANCES IN THE ENVIRONMENT
    Martyn T Smith; Fiscal Year: 2013
    ..The program will be overseen and coordinated by an Administration core (A). ..
  13. Beryllium: Exposure Immune and Genetic Mechanisms
    Lee S Newman; Fiscal Year: 2013
    ..The productivity and continuance demonstrate quality, commitment and ability to work together. PROGRAM AS INTERGRATED EFFORT ..
  14. Environmental Factors in Cardiovascular Disease
    JOEL DANIEL KAUFMAN; Fiscal Year: 2013
    ....