A quantitative-trait analysis of human plasma-dopamine beta-hydroxylase activity: evidence for a major functional polymorphism at the DBH locus

Am J Hum Genet. 2001 Feb;68(2):515-22. doi: 10.1086/318198. Epub 2001 Jan 19.


Dopamine-beta-hydroxylase (D beta H) catalyzes the conversion of dopamine to norepinephrine and is released from sympathetic neurons into the circulation. Plasma-D beta H activity varies widely between individuals, and a subgroup of the population has very low activity levels. Mounting evidence suggests that the DBH structural gene is itself the major quantitative-trait locus (QTL) for plasma-D beta H activity, and a single unidentified polymorphism may account for a majority of the variation in activity levels. Through use of both sequencing-based mutational analysis of extreme phenotypes and genotype/phenotype correlations in samples from African American, European American (EA), and Japanese populations, we have identified a novel polymorphism (--1021C-->T), in the 5' flanking region of the DBH gene, that accounts for 35%--52% of the variation in plasma-D beta H activity in these populations. In EAs, homozygosity at the T allele predicted the very low D beta H-activity trait, and activity values in heterozygotes formed an intermediate distribution, indicating codominant inheritance. Our findings demonstrate that --1021C-->T is a major genetic marker for plasma-D beta H activity and provide new tools for investigation of the role of both D beta H and the DBH gene in human disease.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Substitution
  • Analysis of Variance
  • DNA / chemistry
  • DNA / genetics
  • DNA Mutational Analysis
  • Dopamine beta-Hydroxylase / blood
  • Dopamine beta-Hydroxylase / genetics*
  • Dopamine beta-Hydroxylase / metabolism
  • Gene Frequency
  • Genotype
  • Humans
  • Molecular Sequence Data
  • Phenotype
  • Point Mutation
  • Polymorphism, Restriction Fragment Length
  • Polymorphism, Single Nucleotide
  • Quantitative Trait, Heritable*


  • DNA
  • Dopamine beta-Hydroxylase

Associated data

  • OMIM/223360