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  • Breann Coffaro

Eric Andrew Laurer

Genetic Susceptibility to Biological Responses Following Air Pollution Exposure

Abstract: 

Recent research suggests that ambient air pollution is a risk factor for cardiopulmonary morbidity and mortality. Acute events, such as myocardial infarction, stroke, exacerbation of heart failure, and ventricular arrhythmia, have been found to occur within twenty-four hours of a shortterm, temporary increase in air pollution (often particulate matter less than 2.5 micrometers in aerodynamic diameter, PM2.5). The mechanisms behind these responses remain unclear and difficult to reproduce. The variability in reproducibility could be due to many factors, but the recent focus of many investigators has been in the inherent genetic susceptibility of study populations to air pollution and the response examined. In order to explore underlying mechanisms, scientists have conducted short-term controlled human inhalation exposure studies, as well as examining associations with changes in “ambient” pollutants in the previous few hours, days, or week. These types of studies examine “sub-clinical” outcomes and biomarker changes at the molecular level in response to air pollution by employing a repeated measure, within-subject design.  As part of these ongoing efforts, I propose to assess the presence of candidate SNPs and analyze their predictive effect on acute physiologic and biomarker responses to two hour inhalations of fresh DE and ambient PM2.5 (see Table 2 for candidate genes related to various SNPs).  Available DNA samples from subjects in previous studies will be resequenced/genotyped for specific genomic targets along with samples from additional subjects recruited after initial genetic analyses by EOHSI. We will then assess the relationship between candidate and novel SNPs and biological responses to air pollutants.

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