It has been demonstrated that 5-HTTLPR plays a role in nicotine dependence via mediating rewarding effects in the dopaminergic reward system; two common variants (a 14-repeat short (S) variant having less transcriptional activity and lower serotonin uptake and a 16-repeat long (L) variant) seem to have differential effects. While the S allele has a significant effect on smoking behavior, the L allele contributes more to smoking rate (39). It has been suggested that the differential effects are due to interactions with other polymorphisms, though results are inconclusive (40).
