U. finds genetic link to nicotine addiction

Study says gene variances increase risk of dependency

Published: Friday, July 11 2008 12:09 a.m. MDT

The latest and perhaps the most important reason teenagers should steer clear of using tobacco has been discovered by genetic researchers at the University of Utah.

Common genetic variations affecting nicotine receptors of the human nervous system can seriously increase the chance that those who begin using tobacco daily before age 17 will be severely nicotine-dependent their whole lives, according to findings published today in the journal PloS Genetics.

The results are the first time that gene variances' association with addiction have been correlated with the age at which use of nicotine began.

The variations don't predispose teens to smoke or use tobacco, but those who have the variance and pick up a tobacco habit are much more likely to smoke more and only 5 percent will likely be able to quit as adults, according to findings in the joint study conduct by the U. and the University of Wisconsin-Madison.

Much is yet to be determined regarding the practical application of the new genetic risk factors, but the results at the very least heavily underscore the importance of public health efforts to reduce the number of youths who start smoking, said U. researchers who announced the findings at a news conference Thursday afternoon.

Glen Hanson, a former director of the National Institute on Drug Abuse and head of the Utah Addiction Center, said the discovery opens several possible pathways to designing and targeting prevention and cessation programs.

"This is an incredible discovery," Hanson said. "This isn't the answer, but it opens the door to where we might find the answer. Knowing that we can show the folks who are most at risk will help us toward reducing the use of tobacco and help people avoid the serious consequences of disease associated with it."

The study involved 2,827 long-term European American smokers, recruited in Utah and Wisconsin or referred by the National Heart, Lung and Blood Institute's Lung Health Study. Researchers assessed the level of nicotine dependence for all smokers, and recorded the age they began daily smoking, the number of years they smoked and the average number of cigarettes smoked per day.

DNA samples were taken from all smokers, who were divided into three sets of participants. Researchers tracked the occurrence of common gene variations called single nucleotide polymorphisms, or SNPs. The variations in the SNPs were recorded and compared to those identified in the different sets of participants. SNPs that are inherited together are called a haplotype.

They found that people who began smoking before age 17 and who 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.

One haplotype for the nicotine receptor put European-American smokers at greater risk of heavy nicotine dependence as adults, but only if they began daily smoking before the age of 17.

The high-risk haplotype is common in the three study populations, and European-American populations in general, ranging in frequency from 38 percent to 41 percent.

"We know that people who begin smoking at a young age are more likely to face severe nicotine dependence later in life," said Robert Weiss, a professor of human genetics at the U. and lead author of the study. "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."

Exactly what constituted severe nicotine dependance and heavy use were defined by several guidelines, including how difficult participants said it was to quit, how often they had stopped and then started smoking again and how soon after waking in the morning they smoked their first cigarette of the day. The range varied from several hours later to before their feet touched the floor. That group almost invariably reported they had been smoking since they were teenagers, the researchers said.

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