A Single Nucleotide Polymorphism at DBH, Possibly Associated with Attention-Deficit/Hyperactivity Disorder, Associates with Lower Plasma Dopamine β-Hydroxylase Activity and is in Linkage Disequilibrium with Two Putative Functional Single Nucleotide Polymo

Background The DBH gene regulates plasma dopamine β-hydroxylase activity (pDβH). Two single nucleotide polymorphisms (SNPs), −1021C→T (rs1611115; SNP1) and +1603C→T (rs6271; SNP3), independently influence pDβH. Another SNP, commonly known as DBH Taq1A (rs2519152; SNP2) is associated with attention-deficit/hyperactivity disorder (ADHD) in some (but not all) studies. We tested whether 1) SNP2 associates with pDβH; and 2) whether linkage disequilibrium (LD) between SNP2 and the other SNPs explains that association. Methods Plasma dopamine β-hydroxylase activity and genotypes at the SNPs were determined in Caucasian subjects (n = 418). Associations to pDβH were examined using analyses of variance (ANOVAs) and LD among the SNPs using estimation maximization. Results 1) Each polymorphism analyzed alone associated with pDβH; 2) SNP2 was in strong LD with SNP1 and SNP3, respectively, but there was no significant LD between SNP1 and SNP3; and 3) analyzed jointly, each SNP contributed significantly and uniquely to plasma DβH activity. Conclusions 1) SNP2 associates with pDβH; 2) SNP2 shows LD with SNP1 and SNP3; 3) most of the association between SNP2 and pDβH simply reflects that LD; however, 4) SNP2 also appears to exert a small independent effect on pDβH, suggesting that SNP2, or another variant in LD with it, uniquely influences pDβH.