NICOTINE GENE & SMOKING BEHAVIOR
SAN DIEGO - Many of the forbidden pleasures of the modern day-nicotine, alcohol and over-eating- appear to be linked by common
genetic factors, according to recent studies.
Genetic variables appear to play a key role in every aspect
of nicotine addiction, from the tendency to begin smoking, to the
chances of quitting, reported researchers at the first
conference of the Society for Research on Nicotine and Tobacco.
Evidence is now converging from behavioral studies, twin
studies and molecular genetic research that provides a clearer
understanding of the biobehavioral basis for nicotine dependence.
Ultimately this should lead to the development of improved
methods for assessment and treatment of dependence, said Gary
Swann, Ph.D., of the Stanford Research Institute.
"Behavioral scientists have made great progress in defining
the phenotype and carefully pointing out the variables that have
to be taken into account in describing individual differences in
smoking behaviors. Molecular biologists have made great progress
in identifying an array of nicotinic receptors, the genes
involved and their locations, and other neurochemicals
(particularly dopamine) that may be involved in regulation and
activation of nicotine related behavior," he noted.
Dr. Swan and colleagues analyzed more than 20 studies of
smoking behaviors in monozygotic and dizygotic twins. They found
consistent evidence of genetic influences governing the
developmental stages of smoking (initiation, maintenance,
cessation), smoking intensity (light to heavy), as well as for
level alcohol consumption.
Five years ago, Dr. Ernest Noble and colleagues reported the
discovery of a gene that appeared to be associated with
alcoholism, the D2 dopamine receptor gene (DRD2). Since that time
Dr. Noble has conducted further studies implicating this gene in
behaviors associated with tobacco, cocaine and obesity.
There are two main dopaminergic pathways in brain. The first
begins in the area called the substantia nigra and is involved
with movement. Defects in this part of the brain are associated
with movement disorders such as Parkinson's disease. The second
pathway, the mesolimbic dopamine system, is associated with
"When alcohol, nicotine, cocaine, or food are ingested,
dopamine levels increase in this area. Therefore, we think these
areas are associated with reward and pleasure," noted Dr. Noble,
a professor of psychiatry at UCLA.
The DRD2 gene is found on chromosome 11, in the q22-23
region. There are two alleles of interest, A1 found in 25% of the
population and A2 found in 75%. Studies comparing alcoholics to
controls showed a significantly higher incidence of A1 allele.
The A1 allele is associated with significantly reduced levels of
D2 dopamine receptors in the brain.
"This led us to hypothesize that individuals with the A1
allele may have an inherent deficit of the dopaminergic system.
To compensate for that deficiency, they are high risk for using
alcohol, and other substances which by releasing dopamine
activate these areas," he explained.
Dr. Noble recently completed a study of the association
between this gene with smoking and obesity. This study showed
that male, but not female, smokers with the A1 allele began to
smoke at an earlier age than those with the A2 allele. Also, the
female smokers with the A1 allele were less likely to be obese,
while male smokers with the A1 allele were more likely to be
obese. The study also showed that non-obese female smokers with
the A1 allele had higher levels of anxiety and depression, while
obese female smokers had lower anxiety scores.
"These studies add further support for the role of this gene
in weight and mood in smokers and non-smokers. However, the
differences seen in males and females suggest that besides DRD2
gene, other epigenetic and environmental factors play a role in
contributing to these gender differences," he said.
These findings could point the way to useful therapies for
those attempting to quit smoking or drinking. A recent study with
bromocriptine, a drug that increases levels of DRD2, showed
significant improvements in craving and anxiety among alcoholics
trying to quit.
For more information see: Nature Medicine, 4/4/95, Noble et
al.; Science, 4/26/95, Wehner et al.; or contact the Society for
Research on Nicotine and Tobacco at tel: (301) 251-2792.
Transmitted: 95-05-10 15:15:27 EDT