Abstract 053: Gene Expression Signatures of Tobacco Exposure

Introduction: Cigarette smoking is a cardinal risk factor of coronary heart disease (CHD), yet its gene expression signatures are not well characterized. Hypothesis: We hypothesized that cigarette smoking disturbs expression signatures of many genes, some of which may have long-term implications. Methods: To that end, we analyzed whole-blood gene expression of 2,446 Framingham Heart Study participants (204 current, 1,460 former, and 782 never smokers) and compared gene expression signatures of current vs. never smokers, and former vs. never smokers, adjusting for sex, age, and familial relationship. Smoking status based on self-reported longitudinal data collected over the span of 37 years of observation. P-value and false discovery rate (FDR) were computed for each gene. Results: At FDR<0.05, 1,602 genes were significant in current vs. never smokers. These genes were associated with many pathways, including immune response, response to stress, blood coagulation, platelet activation, and apoptosis. Of the differentially expressed genes, 112 were also associated with smoking in the San Antonio Family Heart Study. At FDR<0.05, 3 genes were significant in former vs. never smokers. These three genes are among the 1,602 genes for current vs. never smokers. Conclusions: Gene expression analysis of current vs. never smokers reveals molecular signatures of tobacco exposure. The differentially expressed genes reflect pathways previously implicated in CHD. Gene expression analysis of former vs. never smokers reveals long-term persisting molecular signatures of tobacco exposure. Table. Top 5 genes in current vs. never smokers and in former vs. never smokers.