Results are based on transcriptional profiles of 1,240 individuals.

A group of researchers report identifying 323 unique genes whose expression levels are significantly correlated with smoking behavior. They note that the results offer insights into system-wide pathological processes induced in response to cigarette smoke exposure by determining its influences at the gene-expression level.

The study is published in BMC Medical Genomics in a paper titled “Transcriptomic epidemiology of smoking: the effect of smoking on gene expression in lymphocytes.”

The investigators obtained genome-wide quantitative transcriptional profiles from 1,240 individuals including 297 current smokers. Using lymphocyte samples, they identified 20,413 transcripts with significantly detectable expression levels including both known and predicted genes. Correlation between smoking and gene-expression levels was determined using a regression model that allows for residual genetic effects.

With a false-discovery rate of 5%, the scientists identified 323 unique genes (342 transcripts) whose expression levels were significantly linked to smoking behavior. These genes showed significant over-representation within a range of functional categories that correspond well with known smoking-related pathologies including immune response, cell death, cancer, natural killer cell signaling, and xenobiotic metabolism.

The results indicate that not only individual genes but entire networks of gene interaction are influenced by cigarette smoking, the researchers point out. This is the largest in vivo transcriptomic epidemiological study of smoking to date and reveals the significant and comprehensive influence of cigarette smoke, as an environmental variable, on the expression of genes, they add.

Jac Charlesworth led the team of researchers from the Southwest Foundation for Biomedical Research. The study was done as part of the long-running San Antonio Family Heart Study in families from the Mexican-American community in San Antonio.

“Previous studies of gene expression as influenced by smoking have been seriously limited in size with the largest of the in vivo studies including only 42 smokers and 43 nonsmokers,” Dr. Charlesworth notes. “We studied 1,240 individuals, including 297 current smokers. Never before has such a clear link between smoking and transcriptomics been revealed, and the scale at which exposure to cigarette smoke appears to influence the expression levels of our genes is sobering.”

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