Clusters of Genetic Variants Linked
to Distinct Treatment Responses for Smoking Cessation
Findings May Help to Match Smokers with Treatments Most Likely
to Help Them Quit
Scientists have identified distinct clusters of genetic markers
associated with the likelihood of success or failure of two smoking
cessation treatments, nicotine replacement therapy (NRT) and the
medication bupropion (Zyban). This study, supported by the National
Institute on Drug Abuse (NIDA) and the National Cancer Institute
(NCI), part of the National Institutes of Health (NIH), was published
in the June issue of the journal Archives of General Psychiatry.
“We have long known that smoking cessation treatments that help
some people fail to help others," says NIDA Director Dr. Nora Volkow. “These
findings shed light on the genetic variations that underlie these
differences in treatment response, and this knowledge may help
make it possible to match smokers with the type or intensity of
smoking cessation treatment most likely to benefit them."
Researchers used a technique known as genome-wide association
scans to compare DNA extracted from the blood of smokers who were
either successful or unsuccessful in quitting using bupropion or
various forms of NRT (e.g., nicotine patch or nasal spray). They
identified clusters of gene variants that were present more frequently
in the successful quitters. Interestingly, the variants were different
in those who were successfully treated with bupropion than in those
who were helped by NRT. For example, a cluster of genes which regulates
the body’s ability to process bupropion was associated with success
on bupropion therapy — but not NRT. The roles of other genes
identified in this study, including several expressed in brain
regions important to learning and memory, are not as well understood.
These genes may be new targets for future research into smoking
cessation medications.
The study was led by Dr. George R. Uhl, chief of NIDA’s molecular
neurobiology research branch in Baltimore, MD, and coauthored by
Caryn Lerman (University of Pennsylvania, Philadelphia, PA), Jed
Rose (Duke University, Durham, NC), and from Brown University,
Ray Niaura (Butler Hospital, Providence, RI), and Sean David (Memorial
Hospital of Rhode Island, Pawtucket, RI). “Our results provide
the first genome-wide evidence that the genetics of successful
smoking cessation with bupropion are different from the genetics
of successful smoking cessation with NRT," says Dr. Uhl. “These
findings suggest that we may be able to improve the success rate
for smoking cessation by using results of simple DNA tests."
The research is part of NIDA’s ongoing commitment to using genome
wide association studies to help develop more targeted prevention
and treatment strategies for addiction. For example, in another
study, also published in the Archives of General Psychiatry in
March, Uhl’s team identified for the first time clusters of genetic
variants associated with vulnerability to methamphetamine dependence,
showing that many of the same genetic variants underlie addiction
to multiple drugs of abuse. The findings suggested that addictions
share common underlying genetic vulnerabilities, providing new
insights into the nature of addiction and suggesting novel approaches
to the treatment of addiction and the prevention of relapse.
For more information go to: http://www.drugabuse.gov/DrugPages/Nicotine.html
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Institutes of Health, U.S. Department of Health and Human Services.
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on NIDA research and other activities can be found on the NIDA
home page at www.drugabuse.gov.
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and supporting basic, clinical and translational medical research,
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