Interactions Between Candidate Cardiovascular Disease Genes, Traffic Proximity, and Left Ventricular Mass: The Multi-Ethnic Study of Atherosclerosis (MESA)

Details

• Personal Author:
  Adar SD ; Arnett D ; Bahrami H ; Barr RG ; Bluemke DA ; Diez Roux AV ; Gill EA ; Kaufman JD ; Rich SS ; Rotter JI ; Sale MM ; Sheppard L ; Szpiro AA ; Van Hee VC ; Wassel C
• Description:
  Rationale: Traffic-related air pollution is associated with cardiovascular disease (CVD) and congestive heart failure, but the mechanisms responsible for this association are unclear. We have demonstrated that residential proximity to major roadways is associated with increased left ventricular mass (LVM), an important intermediate for cardiovascular disease outcomes including heart failure. From a relatively small set of candidate genes, we have also previously identified genes that modify the association between traffic and LVM. We hypothesized that a larger scale candidate gene-environment interaction study would reveal previously unexplored mechanistic pathways responsible for the effect of traffic-related air pollutants on LVM. Methods: A cross-sectional study was conducted using LVM data measured by cardiac MRI between 2000 and 2002 on 1137 participants in MESA. From the total sample of 2882 candidate single-nucleotide polymorphisms (SNPs), we excluded SNPs analyzed in our prior study of gene-traffic interactions and LVM, those with > 5% missing data or minor allele frequency < 5% in any racial group, and those not in Hardy-Weinberg equilibrium (exact p < 0.05) over the entire group, leaving 284 SNPs for this analysis. We used multiple linear regression to evaluate the relationship between residential proximity to roadways (.50 meters versus >150 meters), SNPs (in an additive model), and log LVM, with the product term of SNP*proximity as the interaction coefficient of interest. We adjusted for age, gender, height, weight, study site, race (by ancestry-informative markers), smoking (second-hand smoke exposure, pack-years, current smoking), education, income, alcohol use, diabetes, LDL and HDL cholesterol, and blood pressure. To account for multiple testing, a false discovery rate threshold of 20% (q value < 0.2) was set. Results: After accounting for multiple testing in the fully adjusted model, SNPs in the amiloride-sensitive sodium channel subunit alpha (SCNN1A) and von Willebrand factor (VWF) were associated with significant differences in the association between residential proximity to major roadways and LVM (table). No significant evidence of racial differences in the interactions was observed. Conclusions: We identified common polymorphisms in genes responsible for coagulation and myocardial repolarization that modify associations between proximity to major roadways and LVM. Although pollutants have been associated with changes in vWF, thrombosis, and cardiac repolarization, these genetic factors have not previously been shown to interact with air pollution. 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 Occupational Health Particulate Matter Safety
• Keywords:
  Air Pollution Cardiovascular Disease Cross Sectional Studies Environmental Health Genetic Factors Health Effects Particulates
• ISSN:
  1073-449X
• Document Type:
  Text
• Funding:
  Grant
• Genre:
  Abstract or Summary
• Place as Subject:
  Alabama ; California ; Maryland ; Michigan ; New York ; OSHA Region 10 ; OSHA Region 2 ; OSHA Region 3 ; OSHA Region 4 ; 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:
  181
• NIOSHTIC Number:
  nn:20054879
• Citation:
  Am J Respir Crit Care Med 2010 May; 181(Meeting Abstracts):A1714
• Federal Fiscal Year:
  2010
• Performing Organization:
  University of Washington
• Peer Reviewed:
  True
• Start Date:
  20050701
• Source Full Name:
  American Journal of Respiratory and Critical Care Medicine
• Supplement:
  Meeting Abstracts
• End Date:
  20250630
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:6752d8a0fb79402cb48ffa87ca1615868655e914c94cfd674887cfa1c8a27b969254c49983cbf3cbbf6ac98cb8077f4de8afbfbe0fc3b8d218beebbc7f3e0515
• Download URL:
  https://stacks.cdc.gov/view/cdc/217293/cdc_217293_DS1.pdf
• File Type:
  [PDF - 21.56 KB ]