Aug. 18, 1999 Researchers are delving into the genetics of nicotine addiction for answers
Some people would never think of trying to quit smoking. The daily routine of reaching for a cigarette after morning coffee is too ingrained. Grabbing a smoke after lunch, or after a hard day at the office – there’s nothing quite like a cool long drag, and the expected nicotine buzz. You can quit anytime you like.
For many, however, quitting smoking is next to impossible.
Frank Leone, M.D., assistant professor of medicine at Jefferson Medical College of Thomas Jefferson University, is trying to figure out why some people can "go cold turkey" on cigarettes and nicotine, while others remain slaves to their addiction.
The reasons are many and complex. One of the most intriguing theories says that nicotine addiction is due to a combination of both environmental influences and factors hard-wired into the brain. Some people are simply genetically more susceptible than others to become addicted to the nicotine in cigarettes.
Dr. Leone is using a standard scientific tool, the clinical trial, to attempt to tease out the subtleties of nicotine addiction, and in particular, the potential genetic influence involved in these individual differences. He and his colleagues are looking for 800 pairs of siblings who smoke at least one pack of cigarettes a day and who are nicotine-dependent. Only 400 pairs will be seen at Jefferson; the others will be studied at several other research sites.
In the study, the researchers will sample genetic material from each sibling. "If you share a trait such as eye color, for example, you’re likely to share genes that control them," he says. "We’re taking siblings who share a trait and going backwards and looking for genes in those pairs that are present more frequently than expected.
"What predisposes you to certain behaviors is genetics," he says. "Some people can smoke for years, and one day decide to quit and never go back. Others can try and try and never be able to beat it. The easy answer is, some people have will power and some don’t. But quitting is different for different people. People like to think of themselves as free-willed, but in truth, much of our behavior is wired." Specialists use a number of different techniques to help smokers quit, including behavioral modification and counseling, nicotine replacement therapy with a patch or gum, and drugs. Zyban, an antidepressant, is gaining popularity.
"Despite similarities in nicotine levels in the blood and how people metabolize nicotine, people differ in their addictions," Dr. Leone says. The researchers suspect that the behavioral trait for nicotine dependence is related in part to genetic makeup. It may involve the genes that control how we perceive and process information, he says.
"If we can identify the gene or genes responsible for or contributing to nicotine dependence, it would bring us one step closer to understanding the pathway between nicotine exposure and nicotine dependence. We hope it will tell us more about how to treat nicotine dependence – it’s one step in a long process," he says.
Dr. Leone and his co-workers hope to also conduct a study of unrelated people who share the same trait to see if they share the same genes more frequently than those without the trait.
Scientists know much about the genetics of the biochemistry of nicotine, Dr. Leone explains. There have been "meaningful twin studies showing that identical twins reared apart are more likely to smoke compared to fraternal twins reared apart," he notes. "There’s something dramatic going on that is influenced by biochemistry, but it’s not the only thing going on.
"We might find that there are 10 genes that work together – we don’t know," he says. "Genetics is additive and genes interact. If we get results, they might help support the concept that addictive behavior may be modified.
"Once you have the gene, you can get the biochemical pathway and the brain process of nicotine addiction," Dr. Leone says. "When you understand that, you can talk about intervention. Ultimately, we’d like to find a drug to inhibit a neural pathway."
For more information about enrolling in the trial, please call 215-955-7867 or 1-800-JEFF NOW.
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