We examined two dopaminergic genetic polymorphisms: DRD2 TaqI A and DRD4 48 bp VNTR. The DRD2 TaqI A site is a single nucleotide polymorphism (SNP) with a major A2 allele, and minor A1 allele. The A1+ genotype (heterozygous or homozygous A1) has been most strongly associated with substance abuse, particularly alcoholism, albeit with some controversy [55]. The A1+ genotype has also been related to pathological gambling, novelty seeking, and sensation seeking [45], [55]. The DRD2 TaqI A site is 9.4 kb downstream from the coding region for the dopamine D2 receptor gene. It is not in any known regulatory region, and although the A1 allele is associated with a decrease in dopamine D2 binding and glucose metabolic rates in many brain regions [55]–[57], the mechanism by which it affects DRD2 expression is unknown. The TaqI A polymorphism is also in a nearby kinase gene, the Ankyrin Repeat and Kinase Domain Containing 1 (ANKK1) gene, where it causes a Glutamate→Lysine substitution [58], [59]. The results of the amino acid substitution are not known, but could impact interactions of the ANKK1 protein
