Smoking is a habit that can cost you your life. According to the CDC, "Tobacco use is the leading preventable cause of death in the United States. Cigarette smoking causes an estimated 440,000 deaths, or about 1 of every 5 deaths, each year. This estimate includes 35,000 deaths from secondhand smoke exposure." In addition, "More deaths are caused each year by tobacco use than by all deaths from human immunodeficiency virus (HIV), illegal drug use, alcohol use, motor vehicle injuries, suicides, and murders combined." It is obvious to see why researchers are looking for ways to help those who want to quit smoking. Recently there have been reports in the popular press that if you have a specific type of a gene, you may be able to quit smoking easier than someone who lacks this specific type of gene.
 

DRD2 is the gene that codes for dopamine D2 receptor. It is located on chromosome 11 (see figure below for exact location). Those who carry certain alleles of the gene DRD2 have been shown to be more prone to alcoholism, drug use, and other addictive behaviors. Recently, researchers have found that those with these alleles may be more prone to smoking as well. DRD2 is made up of two alleles, A1 and A2. Therefore you can have three different genotypes if you carry the DRD2 gene (A1/A1, A1/A2, A2/A2).
 
 

Popular Press:

According to a CNN.com article published in 2001, Dr. Paul Cinciripini, the director of the Tobacco Research and Treatment Center at M.D. Anderson conducted a study in which the participants were all given counseling and a nicotine patch (CNN.com 2001). However, some of the subjects were given placebo's while the others were given antidepressants. During the 18 weeks of the study, 25% of those on placebo were able to abstain from smoking while 37% of those on the antidepressants were able to abstain from smoking. Dr. Cinciripini also found that "participants with a certain type of the DRD2 gene were more likely to start smoking again after the 18 weeks." He further stated that, "If you have the A1 allele, you quit (smoking) less often" while those who had the A2 allele responded well to the antidepressants and were able to abstain from smoking more often and for a longer period of time.

Scientific Papers:

A study published in the American Journal of Psychiatry in 2004 looked at trends of smoking progression in adolescents. Audrain-McGovern et al.studied the effects of SLC6A3 and DRD2 but only the effects of DRD2 will be examined here. In addition to examining the smoking progression of the subjects, Audrain-McGovern et al. rated each subject for depression symptoms using the CES-D Scale. They found "of the 615 participants, 412 (67%) had no DRD2 A1 alleles (A2/A2), 184 (30%) had one DRD2 A1 allele (A1/A2), and 19 (3%) had two DRD2 A1 alleles (A1/A1)." They found that "smoking status was not significantly associated with DRD2 genotype." However, when looking at the depression scores there was "a highly significant dose response effect of DRD2 A1 alleles on depressions symptoms." For those adolescents with the A2/A2 genotype their score was 12.4, those with the A1/A2 genotype scored 15.1, and those with the A1/A1 genotype scored the highest on the scale with 16.7. They also found that the number of A1 alleles effected smoking progression, "each A1 allele nearly doubled the odds of smoking progression."

While Dr. Cinciripini's findings are important, the popular article fails to articulate several key features of Dr. Cinciripini's research. A report on Dr. Cinciripini's unpublished data states that the antidepressant venlafaxine was used. Dr. Cinciripini suggested that while there was a more consistent result on smoking cessation using venlafaxine among those with the A2 genotype, some A1 participants also responded positively. Dr. Cinciripini also noted that there is a higher rate of smoking in those that have the A1 allele. He hypothesized that the reason for this higher rate might be that "People with the A1 allele may have lower receptor number or lower binding affinity for dopamine; those with the A1 genotype might be less affected by changes in dopamine availability...If A1 people have deficits in their responsiveness to dopamine, they might compensate for this by using nicotine and other substances more" (Zucker 2001).
 

Conclusion:

While the popular press article is easy to understand and provides hope for those wishing to quit smoking, it is misleading in some respects. The article does not detail the statistical data of the study, nor does it state what form of antidepressants were used and what led researchers to choose antidepressants in the first place. More information needs to be provided as to the roots of using antidepressants. With the scientific paper it was shown that those adolescents with at least one A1 allele were significantly more depressed than those with the A2/A2 genotype. Did Dr. Cinciripini's research look at the depressed state of the adults? Were antidepressants used because it is known that those with the A1 allele are more likely to be depressed? And if so, is the depression the cause of the smoking or is the smoking the cause of depression? These questions were not addressed and are extremely important in deciphering the data.

Furthermore, while the article states that those with the A2 genotype responded better to the antidepressant than those with the A1 genotype it does not state that the A2 genotype is the most prevalent in the population. In addition, the article fails to address that those with the A1 genotype are more likely to continue smoking. While the findings are important they do not address what can be done for those with the A1 genotype, the group that is more likely to continue smoking.
 
 

References:

Audrain-McGovern, et al. 2004 July. Interacting Effects of Genetic Predisposition and Depression on Adolescent Smoking Progression. Am J Psychiatry. 161(7): 1224-1230.

McKusick, Victor A. 2004 June 30. Susceptibility to Tobacco Addiction. OMIM.
< http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=188890 > Accessed 2004 August 30.

Zucker, Mimi. 2001 July. Smoking Cessation Success May Depend on Genetics. PulmonaryReviews.com.
< http://www.pulmonaryreviews.com/jul01/pr_jul01_cessation.html > Accessed 2004 September 14.

1995 May 10. Nicotine Gene & Smoking Behavior. Accessexcellence.org.
< http://www.accessexcellence.org/WN/SUA01/nicotine.html> Accessed 2004 August 30.

2001 April 23. Gene may determine success of smoking cessation. CNN.com/Health.
< http://www.cnn.com/2001/HEALTH/04/23/smoking.cessation/index.html> Accessed 2004 August 30.

2004 February. Tobacco-Related Mortality. Fact sheet. CDC.gov.
< http://www.cdc.gov/tobacco/factsheets/Tobacco_Related_Mortality_factsheet.htm> Accessed 2004 September 14.