title: 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.
abstract: Cigarette smoking, like many addictive behaviors, has been shown to have a genetic component. The dopamine transporter (DAT) 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'sw VNTR, which is a long, G+C-rich repeat.
authors.affiliation: Department of Biobehavioral Health, Center for Developmental and Health Genetics, The Pennsylvania State University, 225 Research Building E, University Park, PA 16802-2321, USA. djv4@psu.edu
authors.forename: David J
authors.initials: DJ
authors.lastname: Vandenbergh
authors.forename: Christina J
authors.initials: CJ
authors.lastname: Bennett
authors.forename: Michael D
authors.initials: MD
authors.lastname: Grant
authors.forename: Andrew A
authors.initials: AA
authors.lastname: Strasser
authors.forename: Richard
authors.initials: R
authors.lastname: O'Connor
authors.forename: Rebecca L
authors.initials: RL
authors.lastname: Stauffer
authors.forename: George P
authors.initials: GP
authors.lastname: Vogler
authors.forename: Lynn T
authors.initials: LT
authors.lastname: Kozlowski
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017931:DNA Primers / Q000235:genetics; D050483:Dopamine Plasma Membrane Transport Proteins; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins / Q000235:genetics; D008875:Middle Aged; D018598:Minisatellite Repeats / Q000235:genetics*; D009419:Nerve Tissue Proteins; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic / Q000235:genetics*; D012044:Regression Analysis; D012907:Smoking; D014029:Tobacco Use Disorder / Q000235:genetics*
chemical_list: D017931:DNA Primers; D050483:Dopamine Plasma Membrane Transport Proteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; C493214:SLC6A3 protein, human