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

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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.

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Authors and Affiliations

  1. Department of Clinical Neuroscience, Psychiatry Section, Karolinska Institute, SE-171 76, Stockholm, Sweden

    Erik G. Jönsson, J. Petter Gustavsson & Göran C. Sedvall

  2. Laboratory of Neurogenetics, Division of Intramural Clinical and Biological Research, National Institute on Alcohol Abuse and Alcoholism, 20892, Rockville, MD, USA

    David Goldman & David A. Nielsen

  3. Institute of Medical Genetics, University of Wales College of Medicine, Heath Park, Cardiff, UK

    Gillian Spurlock & Michael J. Owen

  4. Laboratory of Clinical Studies, Division of Intramural Clinical and Biological Research, National Institute on Alcohol Abuse and Alcoholism, MD 20892, Bethesda, USA

    Markku Linnoila

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  1. Erik G. Jönsson
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  2. David Goldman
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  3. Gillian Spurlock
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  4. J. Petter Gustavsson
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  5. David A. Nielsen
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  6. Markku Linnoila
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  7. Michael J. Owen
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  8. Göran C. Sedvall
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Jönsson, E.G., Goldman, D., Spurlock, G. et al. Tryptophan hydroxylase and catechol-O-methyltransferase gene polymorphisms: relationships to monoamine metabolite concentrations in CSF of healthy volunteers. Eur Arch Psychiatry Clin Neurosci 247, 297–302 (1997). https://doi.org/10.1007/BF02922258

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  • DOI: https://doi.org/10.1007/BF02922258

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