Human Genetics

, Volume 102, Issue 5, pp 533–540

Dopamine β-hydroxylase: two polymorphisms in linkage disequilibrium at the structural gene DBH associate with biochemical phenotypic variation

  • Joseph F. Cubells
  • Daniel P. van Kammen
  • Mary E. Kelley
  • George M. Anderson
  • Daniel T. O’Connor
  • L. H. Price
  • Robert Malison
  • Peter A. Rao
  • Kazuto Kobayashi
  • Toshiharu Nagatsu
  • J. Gelernter
Original investigation

DOI: 10.1007/s004390050736

Cite this article as:
Cubells, J., van Kammen, D., Kelley, M. et al. Hum Genet (1998) 102: 533. doi:10.1007/s004390050736
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Abstract

Levels of the enzyme dopamine β-hydroxylase (DβH) in the plasma and cerebrospinal fluid (CSF) are closely related biochemical phenotypes. Both are under strong genetic control. Linkage and association studies suggest the structural gene encoding DβH (locus name, DΒH) is a major locus influencing plasma activity of DβH. This study examined relationships of DBH genotype determined at two polymorphic sites (a previously described GT repeat, referred to as the DBH STR and a single-base substitution at the 3’ end of DBH exon 2, named DBH*444 g/a), to CSF levels of DβH protein in European-American schizophrenic patients, and to plasma DβH activity in European-American patients with mood or anxiety disorders. We also investigated linkage disequilibrium (LD) between the polymorphisms in the pooled samples from those European-American subjects (n=104). Alleles of DBH*444 g/a were associated with differences in mean values of CSF DβH levels. Alleles at both polymorphisms were associated with plasma DβH activity. Significant LD was observed between respective alleles with similar apparent influence on biochemical phenotype. Thus, allele A3 of the DBH STR was in positive LD with DBH*444a, and both alleles were associated with lower plasma DβH activity. DBH STR allele A4 was in positive LD with DBH*444 g, and both alleles were associated with higher plasma DβH activity. The results confirm that DBH is a major quantitative trait locus for plasma DβH activity, and provide the first direct evidence that DBH also influences CSF DβH levels. Both polymorphisms examined in this study appear to be in LD with one or more functional polymorphisms that mediate the influence of allelic variation at DBH on DβH biochemical phenotypic variation

Copyright information

© Springer-Verlag Berlin Heidelberg 1998

Authors and Affiliations

  • Joseph F. Cubells
    • 1
  • Daniel P. van Kammen
    • 3
  • Mary E. Kelley
    • 3
  • George M. Anderson
    • 4
  • Daniel T. O’Connor
    • 5
  • L. H. Price
    • 2
  • Robert Malison
    • 2
  • Peter A. Rao
    • 1
  • Kazuto Kobayashi
    • 7
  • Toshiharu Nagatsu
    • 8
  • J. Gelernter
    • 1
  1. 1.Psychiatry 116A2, VA Connecticut Health Care System, 950 Campbell Avenue, West Haven, CT 06516, USA Fax: +1-203-937-3897; e-mail: gelernter-joel@cs.yale.eduUS
  2. 2.Department of Psychiatry, Yale University School of Medicine, and VA Connecticut Health Care System, West Haven, CT 06516, USAUS
  3. 3.Department of Psychiatry, University of Pittsburgh School of Medicine, Highland Drive VA Medical Center, Pittsburgh, PA, USAUS
  4. 4.Yale Child Study Center, New Haven, CT 06516, USAUS
  5. 5.Department of Medicine, University of California School of Medicine, San Diego, CA, USAUS
  6. 6.Connecticut Mental Health Center, CT, USAUS
  7. 7.Research and Education Center for Genetic Information, Nara Institute of Science and Technology, Takayama, Ikoma, Nara, JapanJP
  8. 8.Institute for Comprehensive Medical Science, Fujita Health University School of Medicine, Toyoake, JapanJP

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