A genetic variant has been identified which makes smokers more likely to become addicted to nicotine, have an increased lung cancer risk as well as a higher risk of peripheral arterial disease. The study was supported by NIDA (National Institute on Drug Abuse), part of the NIH (National Institutes of Health).

You can read about this in Nature, April 3rd issue.

NIH Director Dr. Elias Zerhouni, said that the study "highlights the advances that are being made in genetics research, which can now identify gene variants that increase the risk of complex bio-behavioral disorders. This finding will help us in our efforts to further reduce the scope and devastating consequences of cigarette smoking."

Dr. Nora Volkow, Director, NIDA, said "These results suggest for the first time that a single genetic variant not only can predispose to nicotine addiction but may also increase sensitivity to extremely serious smoking-related diseases. Additionally, it points to potential targets for new smoking-cessation medications that may be more effective at helping smokers to quit."

The variant is directly linked to two of the known subunits of nicotine receptors, the sites on the surface of many cells in the brain and body that can be bound by nicotine. Nicotine binds to these brain receptors changes take place in cell activity, leading to addiction.

A person who carried this genetic variant is much more likely to be (become) a heavy smoker, much more dependent on nicotine and much less likely to give up smoking successfully.

Dr. Kári Stefánsson, study leader, said "The variant does not increase the likelihood that a person will start smoking, but for people who do smoke it increases the likelihood of addiction." Stefánsson is CEO of deCODE Genetics, a biopharmaceutical company based in Reykjavik, Iceland.

The variant was identified through genome-wide association - DNA samples from over 10,000 Icelandic smokers were analyzed for the presence of over 300,000 genetic markers. They also found that those who carried this variant were closely linked to a higher risk of nicotine dependence, as well as a higher risk of two smoking-related diseases, lung cancer and peripheral arterial disease.

The findings were replicated in populations from five European countries as well as in New Zealand. The scientists estimate that the variant explains 18 percent of cases of lung cancer and 10 percent of cases of peripheral arterial disease in smokers.

"A variant associated with nicotine dependence, lung cancer and peripheral arterial disease"
Thorgeir E. Thorgeirsson, Frank Geller, Patrick Sulem, Thorunn Rafnar, Anna Wiste, Kristinn P. Magnusson, Andrei Manolescu, Gudmar Thorleifsson, Hreinn Stefansson, Andres Ingason, Simon N. Stacey, Jon T. Bergthorsson, Steinunn Thorlacius, Julius Gudmundsson, Thorlakur Jonsson, Margret Jakobsdottir, Jona Saemundsdottir, Olof Olafsdottir, Larus J. Gudmundsson, Gyda Bjornsdottir, Kristleifur Kristjansson, Halla Skuladottir, Helgi J. Isaksson, Tomas Gudbjartsson, Gregory T. Jones, Thomas Mueller, Anders Gottsäter, Andrea Flex, Katja K. H. Aben, Femmie de Vegt, Peter F. A. Mulders, Dolores Isla, Maria J. Vidal, Laura Asin, Berta Saez, Laura Murillo, Thorsteinn Blondal, Halldor Kolbeinsson, Jon G. Stefansson, Ingunn Hansdottir, Valgerdur Runarsdottir, Roberto Pola, Bengt Lindblad, Andre M. van Rij, Benjamin Dieplinger, Meinhard Haltmayer, Jose I. Mayordomo, Lambertus A. Kiemeney, Stefan E. Matthiasson, Hogni Oskarsson, Thorarinn Tyrfingsson, Daniel F. Gudbjartsson, Jeffrey R. Gulcher, Steinn Jonsson, Unnur Thorsteinsdottir, Augustine Kong & Kari Stefansson
Nature 452, 638-642 (3 April 2008) | doi:10.1038/nature06846; Received 17 December 2007; Accepted 25 February 2008
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-- National Institute on Drug Abuse (NIDA)
-- National Institutes of Health (NIH)

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