Comparative sequencing of the proneurotensin gene and association studies in schizophrenia

Austin, J., Hoogendoorn, Bastiaan ORCID: https://orcid.org/0000-0001-9753-169X, Buckland, Paul Robert, Speight, G., Cardno, A., Bowen, Timothy ORCID: https://orcid.org/0000-0001-6050-0435, Williams, Nigel Melville ORCID: https://orcid.org/0000-0003-1177-6931, Spurlock, G., Sanders, R., Jones, L., Murphy, Kevin, McCarthy, G., McGuffin, P., Owen, Michael John ORCID: https://orcid.org/0000-0003-4798-0862 and O'Donovan, Michael Conlon ORCID: https://orcid.org/0000-0001-7073-2379 2000. Comparative sequencing of the proneurotensin gene and association studies in schizophrenia. Molecular Psychiatry 5 (2) , pp. 208-212. 10.1038/sj.mp.4000693

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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 systems1-3 and it is now clear that NT can selectively modulate dopaminergic neurotransmission.2-9 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.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Medicine MRC Centre for Neuropsychiatric Genetics and Genomics (CNGG) Neuroscience and Mental Health Research Institute (NMHRI)
Subjects:	R Medicine > R Medicine (General)
Uncontrolled Keywords:	Alleles, DNA Primers, Exons, Gene Frequency, Genetic Variation*, Genotype, Humans, Neurotensin / cerebrospinal fluid, Neurotensin / genetics*, Polymerase Chain Reaction, Polymorphism, Genetic*, Protein Precursors / genetics*, Schizophrenia / cerebrospinal fluid, Schizophrenia/genetics* Substances DNA Primers,Protein Precursors,proneurotensin,Neurotensin
Additional Information:	Publication Types Comparative Study Research Support, Non-U.S. Gov't Full Text Sources EBSCO ProQuest Other Literature Sources COS Scholar Universe Medical Schizophrenia - MedlinePlus Health Information
Publisher:	Nature Publishing Group
ISSN:	1359-4184
Last Modified:	12 Dec 2022 08:54
URI:	https://orca.cardiff.ac.uk/id/eprint/57918

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