Common Genetic Variation, Residential Proximity to Traffic Exposure, and Left Ventricular Mass: The Multi-Ethnic Study of Atherosclerosis

Details

• Personal Author:
  Adar SD ; Bahrami H ; Barr RG ; Bluemke DA ; Diez Roux A ; Gill EA ; Kaufman JD ; Rich SS ; Rotter JI ; Sale MM ; Sheppard L ; Siscovick DS ; Szpiro AA ; Van Hee VC ; Wassel C
• Description:
  Background: Elevated left ventricular mass (LVM) is a strong predictor of negative cardiovascular outcomes, including heart failure, stroke, and sudden cardiac death. A relationship between close (< 50 m compared with > 150 m) residential proximity to major roadways and higher LVM has previously been described, but the mechanistic pathways that are involved in this relationship are not known. Understanding genetic factors that influence susceptibility to these effects may provide insight into relevant mechanistic pathways. Objective: We set out to determine whether genetic polymorphisms in genes affecting vascular and autonomic function, blood pressure, or inflammation influence the relationship between traffic proximity and LVM. Methods: This was a cross-sectional study of 1,376 genotyped participants in the Multi-Ethnic Study of Atherosclerosis, with cardiac magnetic resonance imaging performed between 2000 and 2002. The impact of tagged single-nucleotide polymorphisms (tagSNPs) and inferred haplotypes in 12 candidate genes (ACE, ADRB2, AGT, AGTR1, ALOX15, EDN1, GRK4, PTGS1, PTGS2, TLR4, VEGFA, and VEGFB) on the relationship between residential proximity to major roadways and LVM was analyzed using multiple linear regression, adjusting for multiple potential confounders. Results: After accounting for multiple testing and comparing homozygotes, tagSNPs in the type 1 angiotensin II receptor (AGTR1, rs6801836) and arachidonate 15-lipoxygenase (ALOX15, rs2664593) genes were each significantly (q < 0.2) associated with a 9-10% difference in the association between residential proximity to major roadways and LVM. Participants with suboptimal blood pressure control demonstrated stronger interactions between AGTR1 and traffic proximity. Conclusions: Common polymorphisms in genes responsible for vascular function, inflammation, and oxidative stress appear to modify associations between proximity to major roadways and LVM. Further understanding of how genes modify effects of air pollution on CVD may help guide research efforts into specific mechanistic pathways. [Description provided by NIOSH]
• Subjects:
  Air Pollution Cardiovascular Diseases Cardiovascular System Cohort Studies Epidemiology Occupational Health Particulate Matter Safety
• Keywords:
  Air Pollution ALOX15 Author Keywords: AGTR1 Biological Effects Cardiac MRI Cardiac Structure Cardiovascular Disease Cohort Studies Gene-environment Interactions Genetic Factors Left Ventricular Mass Oxidative Stress Particulates Traffic

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• ISSN:
  0091-6765
• Document Type:
  Text
• Funding:
  Grant
• Genre:
  Journal Article
• Place as Subject:
  California ; Maryland ; Michigan ; Minnesota ; New York ; OSHA Region 10 ; OSHA Region 2 ; OSHA Region 3 ; OSHA Region 5 ; OSHA Region 9 ; Virginia ; Washington
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  118
• Issue:
  7
• NIOSHTIC Number:
  nn:20054864
• Citation:
  Environ Health Perspect 2010 Jul; 118(7):962-969
• Contact Point Address:
  V.C. Van Hee, Occupational and Environmental Medicine Program, University of Washington, Harborview Medical Center, Box 359739, 325 9th Ave., Seattle, WA 98104 USA
• Email:
  vvanhee@u.washington.edu
• Federal Fiscal Year:
  2010
• Performing Organization:
  University of Washington
• Peer Reviewed:
  True
• Start Date:
  20050701
• Source Full Name:
  Environmental Health Perspectives
• End Date:
  20250630
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:9644f8625dc26dbc0acc9dcd3fc65d5dcdea20f7450c15877cc7ad8195b8f583cc3053035f70041f0a591062a576ffda81cf098b2f7ca2ab8d1b1bb36384bac5
• Download URL:
  https://stacks.cdc.gov/view/cdc/217281/cdc_217281_DS1.pdf
• File Type:
  [PDF - 387.49 KB ]