|NIDA Study Identifies Genes That Might Help
Some People Abstain From Smoking
Findings Move Science Closer to Targeted, Improved
Scientists supported by the National Institute on Drug Abuse (NIDA),
part of the National Institutes of Health, have for the first time
identified genes that might increase a person’s ability to abstain
from smoking. The breakthrough research was conducted by Dr. George
Uhl at NIDA’s Intramural Research Program and a team led by Dr.
Jed Rose at the Center for Nicotine and Smoking Cessation Research
at Duke University Medical Center.
The study, published in the journal BMC Genetics, available
online April 2, brings researchers a step closer toward tailoring
individualized drug therapy for addiction based on an individual’s
unique genetic make-up.
“This research marks the first time we’ve been able to identify
genes involved in the ability to quit smoking,” says NIDA Director
Dr. Nora D. Volkow. “It marks a movement from identifying the genetics
of addiction vulnerability to identifying the genetic basis of
successful abstinence. This knowledge could impact the success
rate of cessation programs by helping health care providers choose
the most appropriate treatment based on individual differences.”
Dr. George Uhl and his colleagues performed a genome wide analysis
on the DNA of two types of nicotine dependent individuals, one
that was able to successfully quit the cigarette smoking behavior
and one that was not.
“We identified 221 genes that distinguished successful quitters
from those who were unsuccessful,” says Dr. Uhl. “We know the functions
of about 187 of these genes, but 34 have functions that are unknown
at present. We also found that at least 62 of the genes that we
had previously identified as playing roles in dependence to other
drugs also contribute to nicotine dependence.”
Genes that harbor variants that contribute to both success in
quitting smoking and in vulnerability to become dependent on multiple
substances include cadherin 13 (a molecule involved in cell adhesion,
which governs how cells recognize and connect to their neighbors)
and a cyclic G-dependent protein kinase gene (that plays a key
role in normal brain development). In addition to genes implicated
in intracellular signaling and intercellular interactions, a number
of genes involved in other processes have also been identified.
While many of the genes identified through this effort make sense
because of their role in supporting new neural connections in the
brain, more research is now needed to understand the actual mechanisms
through which they may increase or reduce the rates of successful
Dr. Uhl says he and his colleagues have replicated this research
in another sample, as he reported at the February 2007 meeting
of the Society for Research on Nicotine and Tobacco.
“These findings provide ample justification for continuing the
search for even more genetic variants associated with smoking cessation
success,” says Dr. Volkow. “We soon may be able to make use of
this information to match treatments with the smokers most likely
to benefit from them.”
The National Institute on Drug Abuse is a component of the National
Institutes of Health, U.S. Department of Health and Human Services.
NIDA supports most of the world’s research on the health aspects
of drug abuse and addiction. The Institute carries out a large
variety of programs to ensure the rapid dissemination of research
information and its implementation in policy and practice. Fact
sheets on the health effects of drugs of abuse and information
on NIDA research and other activities can be found on the NIDA
home page at www.drugabuse.gov.
The National Institutes of Health (NIH) — The Nation's
Medical Research Agency — includes 27 Institutes and
Centers and is a component of the U.S. Department of Health and
Human Services. It is the primary federal agency for conducting
and supporting basic, clinical and translational medical research,
and it investigates the causes, treatments, and cures for both
common and rare diseases. For more information about NIH and
its programs, visit www.nih.gov.