Editors' ChoiceCardiovascular Disease

Smoking Gets Ahold of Your Genes

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Science Translational Medicine  09 May 2012:
Vol. 4, Issue 133, pp. 133ec80
DOI: 10.1126/scitranslmed.3004254

“Pathway to Freedom” and “Become an EX” are among the programs listed by the Centers for Disease Control and Prevention to help quit smoking tobacco. Yet, nicotine exerts a tremendous addictive potential that makes it hard to abandon, even for those having suffered a heart attack, stroke, or pulmonary malignancies—all pathologies linked with smoking. Now, Breitling and colleagues demonstrate that smoking is not only addictive through nicotine but is also associated with methylation patterns in gene products, which implicates smoking in directly altering our genome.

Epigenetic modification of DNA (such as via attachment of methyl groups to certain bases) is an important source of variation and regulation in the genome. Breitling et al. found that methylation of the gene F2RL3—which has been linked with platelet activation and inflammation—was lowest in smokers and highest in nonsmokers. In a prospective study in patients with stable coronary heart disease, lower F2RL3 methylation in smokers and former smokers indicated a worse prognosis with excess cardiovascular mortality as well as overall mortality. The authors found a correlation between F2RL3 methylation intensity and established prognostic markers, including natriuretic peptide, C-reactive protein, and interleukin-6. Current standard medical treatment for coronary artery disease did not affect F2RL3 methylation. The drawbacks of the study design notwithstanding (voluntary participation in motivated patients, mortality data extracted from death certificates only, use of peripheral blood instead of tissue-specific analysis), these data show the potential for smoking to directly regulate our genomes and the importance of F2LR3 methylation intensities as a previously unidentified prognostic marker for mortality. More information on the causal connection between F2LR3 and mortality as well as the pathways mediating methylation of F2LR3 are needed before this gene might evolve as a potential therapeutic target in patients with a history of smoking.

L. P. Breitling et al., Smoking, F2RL3 methylation, and prognosis in stable coronary heart disease. Eur. Heart J. 17 April 2012 (10.1093/eurheartj/ehs091). [Abstract]

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