Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2001 Feb;68(2):515-22.
doi: 10.1086/318198. Epub 2001 Jan 19.

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

C P Zabetian  1 , G M Anderson, S G Buxbaum, R C Elston, H Ichinose, T Nagatsu, K S Kim, C H Kim, R T Malison, J Gelernter, J F Cubells
Affiliations

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

C P Zabetian et al. Am J Hum Genet. 2001 Feb.

Abstract

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.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Distribution of plasma-DβH activity in AA (A), EA (B), and Jp (C). Subjects are grouped in successive 2.5-nmol/min/ml increments. The hatched bar indicates the results for the very low DβH-activity group. The EA and Jp mean activity values differed significantly (P<.01, one-way ANOVA; followed by Dunnett C post-hoc test).
Figure 2
Figure 2
Distribution of square-root plasma-DβH activity, by genotype, at DBH polymorphism −1021C→T in AA (A), EA (B), and Jp (C). Green bars denote T/T homozygotes, red bars denote C/T heterozygotes, and blue bars denote C/C homozygotes. A single C/C homozygote with an extreme activity value of 11.2 square-root nmol/min/ml was omitted from the EA distribution plot, for the purpose of graphical clarity.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

Electronic-Database Information

    1. Database of Single Nucleotide Polymorphisms (dbSNP), http://www.ncbi.nlm.nih.gov/SNP/ (for NCBI-assay ID numbers for 18 new SNPs detected in this study [accession numbers 2418871–2418888])
    1. GenBank, http://www.ncbi.nlm.nih.gov/Genbank/index.html (for DBH genomic sequences [accession numbers AC000404 and AC001227])
    1. HWSIM, http://info.med.yale.edu/genetics/kkidd/programs.html
    1. Online Mendelian Inheritance in Man (OMIM), http://www.ncbi.nlm.nih.gov/Omim/ (for DβH [MIM 223360])

References

    1. Arató M, Bagdy G, Blümel F, Perényi A, Rihmer Z (1983) Reduced serum dopamine-beta-hydroxylase activity in paranoid schizophrenics. Pharmacopsychiatry 16:19–22 - PubMed
    1. Box GEP, Cox DR (1964) An analysis of transformations. J R Stat Soc B 26:211–252
    1. Craig SP, Buckle VJ, Lamouroux A, Mallet J, Craig IW (1988) Localization of the human dopamine beta hydroxylase (DBH) gene to chromosome 9q34. Cytogenet Cell Genet 48:48–50 - PubMed
    1. Cubells JF, Kobayashi K, Nagatsu T, Kidd KK, Kidd JR, Calafell F, Kranzler HR, Ichinose H, Gelernter J (1997) Population genetics of a functional variant of the dopamine beta-hydroxylase gene (DBH). Am J Med Genet 74:374–379 - PubMed
    1. Cubells JF, Kranzler HR, McCance-Katz E, Anderson GM, Malison RT, Price LH, Gelernter J (2000) A haplotype at the DBH locus, associated with low plasma dopamine beta-hydroxylase activity, also associates with cocaine-induced paranoia. Mol Psychiatry 5:56–63 - PubMed

Publication types

Associated data