Gene-Environment Interaction and Coronary Artery Disease: Do OLR1 Gene Polymorphisms Modify the Cardiovascular Effects of Traffic Exposure?

Thesis (Master's)--University of Washington, 2012Background: An association between residential proximity to roadway and coronary artery calcium score (CAC) has been previously described. CAC is a measure of coronary artery calcification that reflects the extent of atherosclerosis. Understanding individual susceptibilities to air pollution's detrimental effects would be improved with a better understanding of genetic influences on the association between air pollution and atherosclerosis. OLR1 is a gene that produces an endothelial cell surface scavenger called the lectin-type oxidized LDL receptor 1(LOX-1). LOX-1scavenges oxidized low-density lipoprotein (oxLDL); its involvement in atherosclerosis progression is supported by prior studies. Demonstrating the role of OLR1 polymorphisms in the air pollution / atherosclerosis relationship may improve understanding of coronary artery disease and air pollution. Methods: Genetic data, CAC score and residential distance to roadway for 5222 participants of the Multi-Ethnic Study of Atherosclerosis (MESA) were used to determine if the relationship between CAC score and distance to major roadway is modified by eleven different OLR1 single nucleotide polymorphisms (SNPs). Linear and logistic regression models were used. Model interaction terms assessed effect modification by the OLR1 polymorphisms. Results: Analysis for main effect of roadway distance on CAC provided no evidence of an association; there was also no evidence of interaction by OLR1 polymorphisms. However, a stratified analysis showed that the Baltimore site demonstrated a significant distance to roadway / CAC association (p-value=0.001). One SNP of the OLR1 gene, rs11053653, demonstrated interaction using only the data from the Baltimore site. The p-value for this interaction was 0.012 (q-value < 0.2). Conclusions: Analysis of eleven SNPs of the OLR1 gene does not provide evidence of a modifying effect in the association between traffic exposure and CAC by OLR1 polymorphisms. One result from a stratified analysis appears statistically significant, but is possibly from a type I error