The dopaminergic system is also believed to play an important role in nicotine dependence, since nicotine increases dopaminergic activity in the brain to induce feelings of pleasure or reward. Candidate genes include: dopamine receptors (D2 and D4), dopamine transporter gene (DAT1), ankyrin repeat and kinase domain containing 1 (ANKK1), tetratricopeptide repeat domain 12 (TTC12), and the serotonin transporter gene (5-HTTLPR). ANKK1 contains a TaqIA1 C>T polymorphism (rs1800497) that has previously been associated with reduced dopamine D2 receptor availability and binding capacities in the brain, which is believed to cause carriers of the allele to compensate for the reduced state of reward following nicotine use. It is also weakly associated with adolescent smoking initiation (9). Dopamine receptor D4 is a G protein-coupled receptor encoded by the DRD4 gene that is activated by the neurotransmitter dopamine. The 48-base pair variable-number-of-tandem-repeats polymorphism in exon III of the DRD4 gene ranges from 2 to 11 repeats. Previous studies have indicated that the longer the repeat, the more dampened the response to dopamine. The DAT1 transporter gene regulates re-uptake of dopamine into presynaptic terminals, terminating
