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Researchers ID Smoking-Related Gene Expression Changes

By a GenomeWeb staff reporter

NEW YORK (GenomeWeb News) – A new study suggests cigarette smoking can alter the expression of hundreds of genes in white blood cells.

A team of researchers from the Southwest Foundation for Biomedical Research and elsewhere did microarray analyses of more than 1,200 individuals, comparing gene expression patterns in white blood cells from smokers and non-smokers. The research, which appeared in BMC Medical Genomics online yesterday, uncovered more than 300 genes that are differentially expressed in smokers — including genes implicated in immune response, cancer, and cell death.

"Never before has such a clear link between smoking and transcriptomics been revealed," lead author Jac Charlesworth — a genetics researcher formerly with SFBF and now at the Menzies Research Institute at the University of Tasmania in Australia — and her co-authors wrote. "And the scale at which exposure to cigarette smoke appears to influence the expression levels of our genes is sobering."

Past studies have implicated cigarette smoking as a risk factor for various human conditions, ranging from heart and lung disease to several types of cancer. But while researchers have detected a handful of carcinogenic compounds in cigarette smoke, the researchers noted, getting a comprehensive picture of how smoking affects the body has been difficult because cigarette smoke contains thousands of compounds that seem to act throughout the body.

To look at how smoking affects gene expression in the blood, Charlesworth and her co-workers used Illumina whole-genome Sentrix Human-6 beadchips to assess the expression of nearly 47,300 transcripts in white blood cells from 1,240 Mexican-American individuals enrolled through the San Antonio Family Heart Study. The study included 297 current smokers.

After doing quality control steps, the team was left with expression data for roughly 20,400 transcripts.

By comparing these expression patterns in the smokers and non-smokers, they were able to identify 342 transcripts — representing 303 known genes and 20 predicted genes — that were differentially expressed in smokers and non-smokers.

Among the genes that were up- or down-regulated in smokers: genes involved in cell toxicity, immune response, cancer, cell death, and the metabolism of foreign chemicals, such as those found in cigarette smoke.

When the team used the Ingenuity Knowledge Base to explore published interactions between differentially expressed genes, they found that 49 of the genes were inter-connected in a network that contained a sub-group of 28 immune and inflammatory response genes.

Given these findings, the researchers explained, it appears smoking impacts gene networks, rather than just individual genes, in the blood and other parts of the body. That, in turn, suggests characterizing these gene interactions in other organs might contribute to a better understanding of how smoking affects the body as a whole.

"It is likely that this observed effect of smoking on transcription has larger implications for human disease risk, especially in relation to the increased risk of a wide variety of cancers throughout the body as a result of cigarette smoke exposure," Charlesworth said in a statement.

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