March 19, 1999

Two recent studies suggest that the propensity for becoming addicted to smoking cigarettes has a significant genetic component.

The studies, which were published in the January issue of Health Psychology, indicate that people carrying a variant of the dopamine transporter gene are less likely to start smoking before age 16 and more likely to quit if they start.

Lead author Caryn Lerman, Ph.D., of Georgetown University Medical Center and colleagues found that people with a dopamine transporter gene variant known as SLC6A3-9 were less likely to start smoking and more likely to quit than people lacking that gene. Lerman and his colleagues looked at 289 smokers and 233 nonsmokers.

The Georgetown study "provides the first evidence that the dopamine transporter genotype is associated with smoking risk, age at smoking initiation, and ability to quit smoking," the authors note. By promoting a better understanding of the interplay of genetic, neuropharmacologic, and environmental factors in smoking, the study "can lead to the development of improved prevention and treatment strategies tailored to the needs of individual smokers."

In another related study, principal investigator Dean Hamer, Ph.D., of the National Cancer Institute and colleagues found that possessing the SLC6A3-9 variant was associated with a lower propensity for novelty seeking, including the need for external stimuli such as nicotine. Hamer and his colleagues examined 1,107 nonsmokers, current smokers, and former smokers.

The NIH study found that "a low level of novelty seeking could be a predictor of smoking cessation," said Hamer. Although those with the dopamine transporter gene variant were 1.5 times more likely to have quit smoking than those without it, the gene is not "a strict determinant of the ability to quit smoking, but rather an influence on an individual's general need and responsiveness to external stimuli, of which cigarette smoking is but one example."

A better understanding of all the variables involved should help scientists develop "more effective, targeted pharmacological and psychoeducational cessation strategies that will take these individual differences into account."

"This study is important for two reasons. First, it provides a clinically relevant confirmation of the theory that dopamine is important in both the acquisition and the cessation of nicotine dependence," said John R. Hughes, M.D., of the Human Behavioral Pharmacology Laboratory and department of Psychiatry at the University of Vermont.

"Second, it clearly suggests genetic status could be used to assign smokers to the optimal therapy; that is, smokers with the genotype associated with decreased dopamine might especially benefit from smoking cessation medications that increase dopamine (for example, bupropion)."