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Saturday, February 17, 2007

Studies Identify DNA Regions Linked to Nicotine Dependence


Americans are bombarded with antismoking messages, yet at least 65 million continue to light up. Genetic factors play an important role in this continuing addiction to cigarettes, suggest scientists at Washington University School of Medicine in St. Louis.

In two studies in the January 2007 issue of Human Molecular Genetics, the scientists show that certain genetic variations can influence smoking behaviors and contribute to a person's risk for nicotine dependence.

The smoking-related genes identified normally facilitate communication between nerve cells in the brain. One gene in particular, the alpha-5 nicotinic cholinergic receptor (CHRNA5) gene, was a very strong indicator of risk for nicotine dependence. Individuals with a specific variation in the gene seemed to have a two-fold increase of developing nicotine dependence once exposed to cigarette smoking. CHRNA5 is from a class of receptors that plays a role in dopamine pathways in the brain, which are linked to a person's experience of pleasure.

The researchers also identified genes related to gamma aminobutyric acid (GABA) receptors, another set of proteins vital to nerve cell function. Both GABA and nicotinic receptors had been suspected of involvement in nicotine addiction, but these findings strengthen those suspicions.

The studies also identified a gene not previously known to be involved with nicotine dependence. Called the Neurexin 1 (NRXN1) gene, it helps regulate the balance between excitatory mechanisms — those that increase communication between nerve cells — and inhibitory mechanisms — those that slow firing between nerve cells.

"An imbalance between excitatory and inhibitory activity in the brain may predispose people to addiction, such as alcoholism, drug dependence or nicotine dependence," says Laura Jean Bierut, M.D., associate professor of psychiatry and principal investigator of both studies. "The Neurexin gene we've identified is really a key factor in the balance between inhibition and excitatory activity in neurons."

Bierut suspects a large number of genes are involved in nicotine dependence, and she says understanding how they work may make it possible to develop new treatments for smoking cessation.

The research team analyzed data from almost 2,000 participants in two ongoing studies. One, called the Collaborative Genetic Study of Nicotine Dependence, is a U.S.-based sample that includes both addicted smokers and "social" smokers from St. Louis, Minneapolis and Detroit. The other is an Australian study of smokers of European ancestry called the Nicotine Addiction Genetics study.

The scientists combined two approaches for analyzing genetic information. One approach scanned the entire human genome for suspicious areas of DNA while the second approach closely examined specific target genes.

"The combination of these two approaches represents the most powerful and extensive study on nicotine dependence to date and is an important step in a large-scale, genetic examination of nicotine dependence," says Elias A. Zerhouni, M.D., the director of the National Institutes of Health, which funded the studies. "As more genomic variations are discovered that are associated with substance abuse, we can better understand addictive disorders."

The researchers identified an area of DNA variation that seems to alter the function of a nicotinic receptor protein. That small variation makes a big difference in risk for nicotine dependence.

Current drug treatments for nicotine dependence continue to be only marginally successful, and Bierut believes using information about genetic traits to tailor medications to individuals could make them significantly more effective. "The type of variant you have at this particular receptor — the alpha-5 nicotinic receptor — may actually predict whether or not you will do well on nicotine replacement therapy," she says.

<---Anyone who's been or is a smoker, knows how hard it is to quit cigarettes. Even after we hear again and agian the risk of lung cancer for some reason we pick up a cigarette, ignoring the cancer statistics. Smokefree seems far away. But eventually, there is a point when quitting smoking makes the most sense.The effect of smoking takes too much of a toll.--->

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1 Comments:

Anonymous Anonymous said...

The links you had were great. I wanted to pass along a site I found that has a few basic videos showing how to quit smoking. I'm not sure if you're interested in how to videos, but I found these useful when I was quitting.

10:00 AM  

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