Two novel variants in the DOPA decarboxylase gene: association with bipolar affective disorder (original) (raw)

Molecular Psychiatry volume 4, pages 545–551 (1999)Cite this article

Abstract

DOPA decarboxylase (DDC), also known as aromatic L-amino acid decarboxylase (AADC), is an enzyme involved in the synthesis of the important neurotransmitters dopamine, norepinephrine, and serotonin. In addition, it participates in the synthesis of trace amines; compounds suggested to act as endogenous modulators of central neurotransmission. Thus, DDC is regarded as a potential susceptibility gene for a variety of neuropsychiatric disorders. The aim of the present study was to examine the role of DDC in bipolar affective disorder (BPAD). By screening 10 individuals for sequence variations in the coding region of the DDC gene as well as in the neuron-specific promoter and 5′ untranslated regions we were able to identify two fairly frequent variants: a 1-bp deletion in the promoter and a 4-bp deletion in the untranslated exon 1. Both deletions affect putative binding sites for known transcription factors, suggesting a possible functional impact at the level of expression. The two variants were applied in an association study including 80 Danish bipolar patients, 112 English bipolar patients, 223 Danish controls, and 349 English controls. Analyzing the combined material, a significant association was found between the 1-bp deletion and BPAD with _P_-values of 0.037 (allelic) and 0.021 (genotypic). The frequency of the 1-bp deletion was 13.3% in patients and 9.4% in controls with a corresponding odds ratio of 1.48 (95% CI: 1.02–2.15). The results presented suggest that DDC may act as a minor susceptibility gene for bipolar affective disorder.

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Authors and Affiliations

  1. Institute of Human Genetics and Danish Centre for Human Genome Research, Aarhus University, Denmark
    A D Børglum & T E Kjeldsen
  2. Mood Disorders Research Unit, Dept A, Psychiatric Hospital in Aarhus, Denmark
    T G Bruun
  3. Department of Psychiatric Demography and Department of Biological Psychiatry, Institute for Basic Psychiatric Research, Psychiatric Hospital in Aarhus, Denmark
    H Ewald
  4. Department of Psychiatric Demography, Institute for Basic Psychiatric Research, Psychiatric Hospital in Aarhus, Denmark
    O Mors
  5. Department of Psychological Medicine, University of Wales College of Medicine, Cardiff, UK
    G Kirov
  6. Department of Neuroscience, Institute of Psychiatry, London, UK
    C Russ
  7. SGDP Centre, Institute of Psychiatry, London, UK
    B Freeman
  8. Department of Psychological Medicine, Institute of Psychiatry, London, UK
    D A Collier
  9. Department of Clinical Biochemistry and Genetics, KKA, Odense University Hospital, Denmark
    T A Kruse

Authors

  1. A D Børglum
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  2. T G Bruun
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  3. T E Kjeldsen
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  4. H Ewald
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  5. O Mors
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  6. G Kirov
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  7. C Russ
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  8. B Freeman
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  9. D A Collier
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  10. T A Kruse
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Corresponding author

Correspondence toA D Børglum.

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Børglum, A., Bruun, T., Kjeldsen, T. et al. Two novel variants in the DOPA decarboxylase gene: association with bipolar affective disorder.Mol Psychiatry 4, 545–551 (1999). https://doi.org/10.1038/sj.mp.4000559

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