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Comparative sequencing of the proneurotensin gene and association studies in schizophrenia

Molecular Psychiatry volume 5, pages 208–212 (2000)Cite this article

Abstract

Neurotensin (NT) is an endogenous tridecapetide1 cleaved from a precursor proneurotensin/ proneuromedin protein. NT localises within dopaminergic neurones in the mesocortical, mesolimbic and nigrostriatal systems1, 2, 3 and it is now clear that NT can selectively modulate dopaminergic neurotransmission.2, 3, 4, 5, 6, 7, 8, 9 These anatomical and functional connections have led to the hypothesis that NT dysfunction might contribute to the pathogenesis of neuropsychiatric disorders in which disordered dopaminergic neurotransmission is suspected, particularly schizophrenia.3 The latter hypothesis has been supported circumstantially by the observation that central administration of NT produces effects similar to those produced by the peripheral administration of atypical antipsychotics,10, 11 and more directly by studies showing levels of NT in cerebral spinal fluid (CSF) is lower in schizophrenics than in controls.12, 13 To allow such hypotheses to be tested, we used denaturing high performance liquid chromatography (DHPLC)14 to identify three sequence variants in the neurotensin gene (NTS) that might alter NT structure or expression. However, using a case-control study design and a novel genotyping system based upon a primer extension protocol and HPLC detection,15 we found no evidence to support the hypothesis that variation in the proneurotensin gene contributes to susceptibility to schizophrenia.

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Acknowledgements

This study was supported by a grant from the Wellcome Trust (Ref 052309). J Austin is funded by a University of Wales College of Medicine Studentship. Grateful thanks to Paul R Dobner, PhD for kindly providing intronic sequence for NTS to allow primer design. We are very grateful for the practical help we received from Professor Michael Krawczak on the use of his HAPMAX program and the advice given on interpretation of its output.

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Authors and Affiliations

  1. Division of Psychological Medicine, University of Wales College of Medicine, Heath Park, Cardiff, CF4 4XN, UK

    J Austin, B Hoogendoorn, P Buckland, G Speight, A Cardno, T Bowen, N Williams, G Spurlock, R Sanders, L Jones, K Murphy, G McCarthy, P McGuffin, M J Owen & M C O'Donovan

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  1. J Austin
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  2. B Hoogendoorn
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  3. P Buckland
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  4. G Speight
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  7. N Williams
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  8. G Spurlock
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  11. K Murphy
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  12. G McCarthy
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  13. P McGuffin
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  14. M J Owen
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  15. M C O'Donovan
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Correspondence to M C O'Donovan.

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Austin, J., Hoogendoorn, B., Buckland, P. et al. Comparative sequencing of the proneurotensin gene and association studies in schizophrenia. Mol Psychiatry 5, 208–212 (2000). https://doi.org/10.1038/sj.mp.4000693

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  • DOI: https://doi.org/10.1038/sj.mp.4000693

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