Dopamine beta-hydroxylase (DBH) catalyzes the conversion of dopamine to norepinephrine (Kaufman and Friedman 1965) and has been associated with ADHD (reviewed in Banaschewski et al. 2010); additionally, a locus near DBH was recently associated with smoking cessation (Furberg et al. 2010). Cubells et al. (2000) investigated the effects of DBH polymorphisms on cocaine-induced paranoia in patients with cocaine dependence/paranoia, and identified a haplotype found more frequently in cocaine-dependent individuals reporting paranoia, that was also associated with low DBH plasma levels in normal subjects (−4784–4803del-444A→G; del-A haplotype). Individuals from the same group later sequenced DBH in eight individuals at the phenotypic extremes for DBH plasma levels, and identified a putative functional polymorphism (−1021C→T; rs1611115; C/T) accounting for 35–52% of phenotype variance in DBH activity (Zabetian et al. 2001); the T allele was associated with low DBH plasma levels, and found to be in positive linkage disequilibrium with the del and A alleles associated with low DBH plasma levels and paranoia in the Cubells et al. (2000) study (Zabetian et al. 2003). A controlled laboratory study was later conducted in which 31
