Gene mutation may be linked to compulsive, risky behavior
By Daily Bruin Staff
March 11, 1998 9:00 p.m.
Thursday, March 12, 1998
Gene mutation may be linked to compulsive, risky behavior
HEALTH: Presence of DRD2 form heightens drive to find
pleasure
By Kathryn Combs
Daily Bruin Staff
In the face of social pressures against smoking and recent
anti-smoking laws, those who claim they don’t have the willpower to
quit smoking may have yet another excuse: it could be genetic.
According to Dr. Ernest Noble, director of the UCLA Alcohol
Research Center, an individual’s affinity for smoking may have a
genetic cause.
In the United States each year, more than 400,000 people die of
smoking-related causes and approximately 160,000 die of causes
related to lung cancer.
In an article published in the Journal of the National Cancer
Institute earlier this month, Noble claims a genetic mutation could
be responsible for compulsive behaviors such as smoking, drinking
and drug use.
In 1990, Noble and colleagues discovered a genetic mutation on
the DRD2 gene. The D2 dopamine receptor (DRD2) gene is responsible
for the production of dopamine in the brain.
When an individual experiences pleasure, dopamine is the
molecule that is responsible for stimulating this response in the
brain, Noble explained.
Noble and his colleagues found that the A1 and B1 alleles in the
DRD2 gene are responsible for compulsive behavior.
In 1990, the DRD2 gene was found to be associated with the
prevalence of severe alcoholism. Since then, it has been
hypothesized that the gene is linked to cocaine abuse, cigarette
smoking and other polysubstance abuse.
"We found that this gene variant was found in people who were
active smokers, and found less of a prevalence in people who had
quit smoking," Noble said.
"There was also a very low prevalence in those who are
non-smokers or who had never smoked," he added.
Dr. David Comings, with the City of Hope Hospital, has conducted
similar research and says that not only are Noble’s findings
plausible, they are probable.
"We found that this gene was present in 48 percent of a group of
331 individuals, as opposed to 25 percent in our control group,"
Comings said.
According to Noble, smokers whose genetic makeup contain a minor
form of the DRD2 gene are more likely not only to begin smoking
earlier in their lives, but are also likely to have more difficult
time trying to kick the habit.
"If you have the gene form, your brain makes fewer dopamine
receptors," Noble said. "These are the pleasure areas of the brain.
We hypothesized that these individuals don’t feel the normal
pleasures in life."
As a result, individuals with this genetic predisposition seek
out activities which heighten the stimulation of dopamine-producing
areas in the brain, such as smoking and eating.
"(However), not everyone who is a smoker has this gene form, and
we call those environmental types," Noble said.
"We found when you measure behavior, such as personality, those
individuals that have the minor form of this gene are risk-takers,"
Noble said, explaining that although an individual may be
genetically susceptible to life-threatening behaviors such as
substance abuse, these individuals do not always exhibit negative
types of behavior.
In fact, Noble said that in a long-term study of children and
adults who possess the minor form of the DRD2 allele and who do not
exhibit addictive behaviors related to substance abuse, many take
risks in other ways such as bungee jumping and parachuting. They
are novelty seekers, according to Noble.
"It’s like there are two sides of the coin," he said.
"There is a dark side which gets you to use alcohol and gets you
into accidents and drugs … and there is the other side which
makes you look for new things," Noble said. "Perhaps some of our
greatest explorers like Magellan or Cooke could have had this."
According to Dr. Donald Tashkin, a professor with the UCLA
School of Medicine, this investigation may be helpful in designing
more effective treatment for problems with substance abuse.
"If we could identify a genetic basis for the use of addictive
drugs, we might be able to develop more effective pharmacological
approaches as well as treatment of addiction,"he added.
Dr. Comings agreed. Researchers are already exploring the
possibilities. "Agents which act on these dopamine receptors can
probably help," Comings said.
The development of drugs to treat this lack of dopamine is
currently being conducted.
"We need a targeted approach," Noble said. "If you have the
genetic form, while the environmental approach may be helpful, I
think you may eventually have to develop drugs to help."
"You may be able to target such individuals … (to) prevent
them from initializing use, or in assisting them in the cessation
of use," he added.PATIL ARMENIAN
Dr. Ernest Noble believes smoking may be genetic.
