and internalization, consistent with data in human abstinent cocaine abusers that show decreased D2 receptor availability in the striatum [28]. To our knowledge, this is the first study investigating NCS-1 as a risk gene for CA. Earlier, Dahl et al. (2006) reported an interesting pharmacogenetic interaction between polymorphisms in two genes encoding components of DRD2 and NCS-1 in a smoking cessation trial with nicotine replacement therapy (NRT) [9]. They observed a statistically significant interaction between a common variant in the NCS-1 gene (rs1054879) and a functional variant in the DRD2 promoter and treatment outcome. Those individuals with the DRD2-141Ins/Del and the A allele of NCS-1 rs1054879 showed greater abstinence at end of treatment, strengthening the potential role of dopamine interacting proteins and substance use phenotypes. It is likely that many of our cocaine addicted individuals are co-addicted to nicotine as this was not used as an exclusion criterion for this study. Therefore, our findings may reflect an association with nicotine addiction or addiction in general, an important aspect that should be considered in the interpretation of results.
