title: 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.
abstract: 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.
authors.affiliation: Department of Psychiatry, Yale University School of Medicine and VA Connecticut Healthcare System, New Haven, Connecticut, USA.
authors.forename: Yilang
authors.initials: Y
authors.lastname: Tang
authors.forename: Sarah G
authors.initials: SG
authors.lastname: Buxbaum
authors.forename: Irwin
authors.initials: I
authors.lastname: Waldman
authors.forename: George M
authors.initials: GM
authors.lastname: Anderson
authors.forename: Cyrus P
authors.initials: CP
authors.lastname: Zabetian
authors.forename: Michael D
authors.initials: MD
authors.lastname: Köhnke
authors.forename: Joseph F
authors.initials: JF
authors.lastname: Cubells
mesh_terms: D000328:Adult; D000704:Analysis of Variance; D001289:Attention Deficit Disorder with Hyperactivity / Q000235:genetics*; D004299:Dopamine beta-Hydroxylase / Q000097:blood* / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D044465:White People
chemical_list: D004299:Dopamine beta-Hydroxylase