TY - JOUR
T1 - The effects of the DRD2 polymorphism on smoking cessation and negative affect
T2 - Evidence for a pharmacogenetic effect on mood
AU - Cinciripini, Paul M.
AU - Wetter, David W.
AU - Tomlinson, Gail E.
AU - Tsoh, Janice Y.
AU - De Moor, Carl A.
AU - Cinciripini, Lynn G.
AU - Minna, John D.
AU - Baile, Walter S.
PY - 2004/4
Y1 - 2004/4
N2 - This study evaluated the relationship between smoking cessation treatment outcome and the DRD2 polymorphism. Participants were 134 smokers who took part in a larger clinical trial evaluating the effects of an antidepressant medication (venlafaxine or placebo) plus standard care (brief counseling and nicotine replacement therapy). Venlafaxine is an antidepressant that inhibits the reuptake of serotonin and norepinephrine. A1 smokers were expected to quit significantly less often on placebo, although the abstinence rates between A1s and A2s on active drug were not expected to differ (i.e., an interaction between genotype and drug was hypothesized). In addition, antidepressant therapy was expected to have a similar genotype × treatment interaction on negative affect reduction. The results showed that smokers carrying the DRD2 A1 allele (A1/A1/A2) quit significantly less often than the homozygous A2s (OR=1.54, 95% CI=1.01-2.36). No interaction with treatment was observed. A significant pharmacogenetic effect of the drug on negative mood while quitting also was noted. Smokers absent the A1 allele (A2/A2) responded to the drug with a substantial reduction in negative affect, whereas those with the A1 allele showed no significant reduction in negative mood, F(1, 130) = 5.95, p =.01. These results are contrary to expectations and suggest that although A1s may have more difficulty quitting, adding venlafaxine does not improve abstinence or mood. However, the results for the A2s provide evidence for a genotype-specific response to a pharmacological intervention, which could have implications for the development of future treatments.
AB - This study evaluated the relationship between smoking cessation treatment outcome and the DRD2 polymorphism. Participants were 134 smokers who took part in a larger clinical trial evaluating the effects of an antidepressant medication (venlafaxine or placebo) plus standard care (brief counseling and nicotine replacement therapy). Venlafaxine is an antidepressant that inhibits the reuptake of serotonin and norepinephrine. A1 smokers were expected to quit significantly less often on placebo, although the abstinence rates between A1s and A2s on active drug were not expected to differ (i.e., an interaction between genotype and drug was hypothesized). In addition, antidepressant therapy was expected to have a similar genotype × treatment interaction on negative affect reduction. The results showed that smokers carrying the DRD2 A1 allele (A1/A1/A2) quit significantly less often than the homozygous A2s (OR=1.54, 95% CI=1.01-2.36). No interaction with treatment was observed. A significant pharmacogenetic effect of the drug on negative mood while quitting also was noted. Smokers absent the A1 allele (A2/A2) responded to the drug with a substantial reduction in negative affect, whereas those with the A1 allele showed no significant reduction in negative mood, F(1, 130) = 5.95, p =.01. These results are contrary to expectations and suggest that although A1s may have more difficulty quitting, adding venlafaxine does not improve abstinence or mood. However, the results for the A2s provide evidence for a genotype-specific response to a pharmacological intervention, which could have implications for the development of future treatments.
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U2 - 10.1080/14622200410001676396
DO - 10.1080/14622200410001676396
M3 - Article
C2 - 15203796
AN - SCOPUS:2542495997
SN - 1462-2203
VL - 6
SP - 229
EP - 239
JO - Nicotine and Tobacco Research
JF - Nicotine and Tobacco Research
IS - 2
ER -