Several genes have been implicated in various aspects of cocaine addiction. These include dopaminergic single nucleotide polymorphisms (SNPs) in DRD2/ANKK149 as well as neighboring NCAM1 and TTC12, CALCYON,50 dopamine beta-hydroxylase (DBH)51 and catechol-O-methyltransferase (COMT);52 opioidergic genes such as POMC;53 CNR1;54 orthologs of genes regulating circadian rhythms (CLOCK, PER1, and PER2);55 tryptophan hydroxylase 2 (TPH2)56 and others gleaned from linkage studies (for example, alpha-endomannosidase (MANEA))57—a majority of these await replication. Of particular interest, the functional SNP in the CHRNA5/A3/B4 cluster on chromosome 15, rs16969968, (extensively discussed in later sections and in Table 1 with reference to nicotine dependence) has been found to be associated with cocaine dependence in two independent studies—paradoxically, the allelic variant of this marker that confers risk for nicotine dependence appears to afford protection from cocaine addiction.58, 59
