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

• Published in: Environmental health perspectives 2010-07, Vol.118 (7), p.962-969
• Main Authors: Van Hee, Victor C., Adar, Sara D., Szpiro, Adam A., Barr, R. Graham, Roux, Ana Diez, Bluemke, David A., Sheppard, Lianne, Gill, Edward A., Bahrami, Hossein, Wassel, Christina, Sale, Michele M., Siscovick, David S., Rotter, Jerome I., Rich, Stephen S., Kaufman, Joel D.
• Format: Article
• Language: English
• Subjects: Aged; Aged, 80 and over; Air; Air pollution; Air Pollution - statistics & numerical data; Atherosclerosis; Atherosclerosis (general aspects, experimental research); Biological and medical sciences; Blood and lymphatic vessels; Blood pressure; Cardiology. Vascular system; Cross-Sectional Studies; Demographic aspects; Environment. Living conditions; Environmental aspects; Environmental Exposure; Environmental pollutants toxicology; Epidemiology; Female; Genetic aspects; Genetic Predisposition to Disease - genetics; Genetic Variation; Genotype; Haplotypes; Haplotypes - genetics; Health aspects; Heart ventricle, Left; Humans; Hypertrophy, Left Ventricular - epidemiology; Hypertrophy, Left Ventricular - genetics; Hypertrophy, Left Ventricular - pathology; Identification and classification; Linear Models; Magnetic Resonance Imaging; Male; Medical genetics; Medical sciences; Medications; Mesas; Middle Aged; Polymorphism, Single Nucleotide - genetics; Public health. Hygiene; Public health. Hygiene-occupational medicine; Roads; Toxicology; Traffic; Vehicle Emissions
• ISSN: 0091-6765; 1552-9924
• DOI: 10.1289/ehp.0901535

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.