Smoking status and the human dopamine transporter variable number of tandem repeats (VNTR) polymorphism: Failure to replicate and finding that never-smokers may be different

Cigarette smoking, like many addictive behaviors, has been shown to have a genetic component. The dopamine transporter (DA7) gene (SLC6A3) encodes a protein that regulates synaptic levels of dopamine in the brain and is a candidate gene for addictive behaviors. We have collected smoking information from a national probability sample of 3383 adult volunteers contacted via a random-digit dialing telephone interview. A subset of individuals provided DNA from cheek swabs returned via the mail for subsequent genetic analysis of self-reported smoking behavior. DNA samples were genotyped at a variable number of tandem repeats (VNTR) polymorphism in the 3′-untranslated region of the DAT gene. If we classify smokers as non- (<100 cigarettes), former and current, we fail to replicate both Lerman et al. (Health Psychology 18:14-20, 1999) and Sabol et al. (Health Psychology 18:7-13, 1999) and support the absence of effects found by Jorm et al. (American Journal of Medical Genetics (Neuropsychiatric Genetics) 96:331-334, 2000). When we distinguish between never-smokers (no cigarettes ever) and non-smokers (1-99 in lifetime), we find a reliable trend essentially in the opposite direction from Lerman et al. (1999), with the 10-copy allele being more frequent in never-smokers. Biobehavioral research on cigarette smoking should distinguish between never- and non-smokers. We have also developed an improved set of polymerase chain reaction conditions to increase the frequency of successful amplification of DAT's VNTR, which is a long, G+C-rich repeat.