Genetic polymorphisms in dopamine-related genes and smoking cessation in women: a prospective cohort study.
BACKGROUND
Genes involved in dopaminergic neurotransmission have been suggested as candidates for involvement in smoking behavior. We hypothesized that alleles associated with reduced dopaminergic neurotransmission would be more common in continuing smokers than among women who quit smoking.


METHODS
The study included 593 women aged 26-65 years who participated in a twelve month smoking cessation trial conducted in 1993-1994. Participants were contacted three years after the trial to obtain updated smoking history and biological specimens. Seven polymorphisms were assessed in genes involved in dopamine synthesis (tyrosine hydroxylase [TH]), receptor activation (dopamine receptors [DRD2, DRD3, DRD4]), reuptake (dopamine transporter [SLC6A3]), and metabolism (catechol-o-methyltransferase [COMT]). Smoking cessation was assessed as "short-term" quitting (abstinence for the seven days before the conclusion of the trial) and "long-term" quitting (abstinence for the six months before a subsequent interview conducted several years later).


RESULTS
We observed no association of any polymorphism with either short- or long-term quitting. Although some relative risk estimates were consistent with weak associations, either the direction of effect was opposite of that hypothesized, or results of the short- and long-term cessation endpoints differed. However, effect modification on smoking cessation was observed between DRD2 Taq1A and SLC6A3 VNTR polymorphisms, DRD3 Ser/Gly and d,1-fenfluramine, and DRD4 VNTR and d,1-fenfluramine.


CONCLUSIONS
Although these results fail to support prior findings of independent associations of these polymorphisms with smoking status, our exploratory findings suggestive of gene-gene and gene-treatment interactions warrants further investigation.
Ton
Thanh G N
TG
Department of Neurology, University of Washington, Box 359775, 325 Ninth Ave, Suite 3EH70, Seattle, WA 98195-9775, USA. thanhton@u.washington.edu
Rossing
Mary Anne
MA
Bowen
Deborah J
DJ
Srinouanprachan
Sengkeo
S
Wicklund
Kristine
K
Farin
Federico M
FM