A single nucleotide polymorphism at DBH, possibly associated with attention-deficit/hyperactivity disorder, associates with lower plasma dopamine beta-hydroxylase activity and is in linkage disequilibrium with two putative functional single nucleotide polymorphisms

Biol Psychiatry. 2006 Nov 15;60(10):1034-8. doi: 10.1016/j.biopsych.2006.02.017. Epub 2006 Apr 17.


Background: The DBH gene regulates plasma dopamine beta-hydroxylase activity (pDbetaH). Two single nucleotide polymorphisms (SNPs), -1021C-->T (rs1611115; SNP1) and +1603C-->T (rs6271; SNP3), independently influence pDbetaH. 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 pDbetaH; and 2) whether linkage disequilibrium (LD) between SNP2 and the other SNPs explains that association.

Methods: Plasma dopamine beta-hydroxylase activity and genotypes at the SNPs were determined in Caucasian subjects (n = 418). Associations to pDbetaH were examined using analyses of variance (ANOVAs) and LD among the SNPs using estimation maximization.

Results: 1) Each polymorphism analyzed alone associated with pDbetaH; 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 DbetaH activity.

Conclusions: 1) SNP2 associates with pDbetaH; 2) SNP2 shows LD with SNP1 and SNP3; 3) most of the association between SNP2 and pDbetaH simply reflects that LD; however, 4) SNP2 also appears to exert a small independent effect on pDbetaH, suggesting that SNP2, or another variant in LD with it, uniquely influences pDbetaH.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Analysis of Variance
  • Attention Deficit Disorder with Hyperactivity / genetics*
  • Dopamine beta-Hydroxylase / blood*
  • Dopamine beta-Hydroxylase / genetics*
  • European Continental Ancestry Group
  • Female
  • Gene Frequency
  • Genetic Predisposition to Disease*
  • Genotype
  • Humans
  • Linkage Disequilibrium*
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide / genetics*


  • Dopamine beta-Hydroxylase