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Tryptophan hydroxylase and catechol-O-methyltransferase gene polymorphisms: relationships to monoamine metabolite concentrations in CSF of healthy volunteers

  • Erik G. Jönsson
  • David Goldman
  • Gillian Spurlock
  • J. Petter Gustavsson
  • David A. Nielsen
  • Markku Linnoila
  • Michael J. Owen
  • Göran C. Sedvall
Original Paper

Abstract

Concentrations of monoamine metabolites (MM) in lumbar cerebrospinal fluid (CSF) have been used extensively as indirect estimates of monoamine turnover in the brain. We investigated possible relationships between DNA polymorphisms in the tryptophan hydroxylase (TPH) and catechol-O-methyltransferase (COMT) genes and CSF concentrations of 5-hydroxyindoleacetic acid (5-HIAA), homovanillic acid (HVA), and 3-methoxy-4-hydroxyphenylglycol (MHPG) in healthy volunteers (n = 66). Lower CSF 5-HIAA levels were found in men with the TPH U allele (p = 0.005), but not in women. A similar but less significant pattern was observed for CSF HVA. No relationship was found between the TPH polymorphism and CSF MHPG. COMT genotypes did not relate significantly to MM concentrations. The results suggest that TPH genotypes participate differentially in the regulation of serotonin turnover rate under presumed steady state in the central nervous system of men. Due to the uncertain functional relevance of the DNA polymorphism investigated and the many calculations performed, the results should be interpreted with caution until replicated.

Key words

Tryptophan hydroxylase gene Catechol-O-methyltransferase gene Monoamine metabolites (HVA, 5-HIAA, MHPG) Cerebrospinal fluid 

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Copyright information

© Springer-Verlag 1997

Authors and Affiliations

  • Erik G. Jönsson
    • 1
  • David Goldman
    • 2
  • Gillian Spurlock
    • 3
  • J. Petter Gustavsson
    • 1
  • David A. Nielsen
    • 2
  • Markku Linnoila
    • 4
  • Michael J. Owen
    • 3
  • Göran C. Sedvall
    • 1
  1. 1.Department of Clinical Neuroscience, Psychiatry SectionKarolinska InstituteStockholmSweden
  2. 2.Laboratory of Neurogenetics, Division of Intramural Clinical and Biological ResearchNational Institute on Alcohol Abuse and AlcoholismRockvilleUSA
  3. 3.Institute of Medical GeneticsUniversity of Wales College of MedicineHeath ParkUK
  4. 4.Laboratory of Clinical Studies, Division of Intramural Clinical and Biological ResearchNational Institute on Alcohol Abuse and AlcoholismBethesdaUSA

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