Common genetic variations increase risk of life-long nicotine addiction for young smokers

Common genetic variations affecting nicotine receptors in the nervous system can significantly increase the chance that European Americans who begin smoking by age 17 will struggle with life-long nicotine addiction. Published July 11 in the open-access journal PLoS Genetics, this research - led by scientists at the University of Utah together with colleagues from the University of Wisconsin - highlights the importance of preventing early exposure to tobacco through public health policies.

These common genetic variations, or single nucleotide polymorphisms (SNPs), are changes in a single unit of DNA. A haplotype is a set of SNPs that are statistically linked. The researchers found that one haplotype for the nicotine receptor put European American smokers at a greater risk of heavy nicotine dependence as adults, but only if they began daily smoking before the age of 17. A second haplotype actually reduced the risk of adult heavy nicotine dependence for people who began smoking in their youth.

The researchers studied 2,827 long-term European American smokers, recruited in Utah and Wisconsin, and to the National Heart, Lung, and Blood Institute's Lung Health Study. They assessed the level of nicotine dependence for all smokers, recording the age they began smoking daily, the number of years they smoked, and the average number of cigarettes smoked per day. DNA samples were taken from all smokers, and the researchers recorded the occurrence of common SNPs, grouped into four haplotypes, which had been identified earlier in a subset of participants.

They found that people who began smoking before the age of 17 and possessed two copies of the high-risk haplotype had from a 1.6-fold to almost 5-fold increase in risk of heavy smoking as an adult. For people who began smoking at age 17 or older, presence of the high-risk haplotype did not significantly influence their risk of later addiction.

Although the authors caution that different haplotype frequencies would likely be observed in different ethnic populations, Robert Weiss, Ph.D., professor of human genetics at the University of Utah and lead author of the study, explains: "We know that people who begin smoking at a young age are more likely to face severe nicotine dependence later in life. This finding suggests that genetic influences expressed during adolescence contribute to the risk of lifetime addiction severity produced from the early onset of tobacco use."

"This study adds to recent advances in understanding how genetic variation can affect susceptibility to nicotine addiction, success or failure of smoking cessation treatments, and the risk of disease associated with tobacco use," says National Institute on Drug Abuse (NIDA) Director Dr. Nora Volkow. "As we learn more about how both genes and environment play a role in smoking, we will be able to better tailor both prevention and cessation programs to individuals." The study was funded in part by NIDA and the National Heart, Lung, and Blood Institute (NHLBI), parts of the National Institutes of Health (NIH).