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Association of the leucine-7 to proline-7 variation in the signal sequence of neuropeptide Y with major depression

Published online by Cambridge University Press:  24 June 2014

Pernille Koefoed ,
David P.D. Woldbye ,
Thomas v. O. Hansen ,
Lene F. Eplov ,
Søren H. Christiansen ,
Ole Mors ,
Lars V. Kessing ,
Thomas Werge ,
Katja Kaipio  and
Ullamari Pesonen
...Show all authors
Pernille Koefoed*
Affiliation:
Laboratory of Neuropsychiatry, Department of Neuroscience and Pharmacology, University of Copenhagen, Copenhagen, Denmark Department of Clinical Biochemistry, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark Mental Health Centre Copenhagen, Rigshospitalet, Copenhagen, Denmark
David P.D. Woldbye
Affiliation:
Laboratory of Neuropsychiatry, Department of Neuroscience and Pharmacology, University of Copenhagen, Copenhagen, Denmark Mental Health Centre Copenhagen, Rigshospitalet, Copenhagen, Denmark
Thomas v. O. Hansen
Affiliation:
Department of Clinical Biochemistry, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
Lene F. Eplov
Affiliation:
Research Centre for Prevention and Health, Copenhagen University Hospital Glostrup, Glostrup, Denmark and Research Unit for Psychiatric Rehabilitation, Mental Health Centre Ballerup, Ballerup, Denmark
Søren H. Christiansen
Affiliation:
Laboratory of Neuropsychiatry, Department of Neuroscience and Pharmacology, University of Copenhagen, Copenhagen, Denmark
Ole Mors
Affiliation:
Centre for Psychiatric Research, Aarhus University Hospital, Risskov, Denmark
Lars V. Kessing
Affiliation:
Mental Health Centre Copenhagen, Rigshospitalet, Copenhagen, Denmark
Thomas Werge
Affiliation:
Research Institute of Biological Psychiatry, Mental Health Centre St. Hans Hospital, Roskilde, Denmark
Katja Kaipio
Affiliation:
Department of Pharmacology, Drug Development and Therapeutics, University of Turku, Turku, Finland
Ullamari Pesonen
Affiliation:
Department of Pharmacology, Drug Development and Therapeutics, University of Turku, Turku, Finland
Thomas Fahmy
Affiliation:
Mental Health Centre Copenhagen, Rigshospitalet, Copenhagen, Denmark
Erling Mellerup
Affiliation:
Laboratory of Neuropsychiatry, Department of Neuroscience and Pharmacology, University of Copenhagen, Copenhagen, Denmark
Klaus D. Jakobsen
Affiliation:
Research Institute of Biological Psychiatry, Mental Health Centre St. Hans Hospital, Roskilde, Denmark Mental Health Centre Hvidovre, Hvidovre, Denmark
Elsebeth S. Hansen
Affiliation:
Mental Health Centre Copenhagen, Rigshospitalet, Copenhagen, Denmark
Gitte M. Knudsen
Affiliation:
Center for Integrated Molecular Brain Imaging, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
Jens D. Bukh
Affiliation:
Mental Health Centre Copenhagen, Rigshospitalet, Copenhagen, Denmark
Camilla Bock
Affiliation:
Mental Health Centre Copenhagen, Rigshospitalet, Copenhagen, Denmark
Camilla Lindberg
Affiliation:
Laboratory of Neuropsychiatry, Department of Neuroscience and Pharmacology, University of Copenhagen, Copenhagen, Denmark
Ann S. Kristensen
Affiliation:
Centre for Psychiatric Research, Aarhus University Hospital, Risskov, Denmark
Henrik Dam
Affiliation:
Mental Health Centre Copenhagen, Rigshospitalet, Copenhagen, Denmark
Merete Nordentoft
Affiliation:
Mental Health Centre Copenhagen, Rigshospitalet, Copenhagen, Denmark
Thomas D. Als
Affiliation:
Centre for Psychiatric Research, Aarhus University Hospital, Risskov, Denmark
August G. Wang
Affiliation:
Mental Health Centre Amager, Copenhagen, Denmark
Ulrik Gether
Affiliation:
Molecular Neuropharmacology Group and Center for Pharmacogenomics, Department of Neuroscience and Pharmacology, University of Copenhagen, Copenhagen, Denmark
Jens F. Rehfeld
Affiliation:
Department of Clinical Biochemistry, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
Tom G. Bolwig
Affiliation:
Laboratory of Neuropsychiatry, Department of Neuroscience and Pharmacology, University of Copenhagen, Copenhagen, Denmark
*
Pernille Koefoed, Laboratory of Neuropsychiatry, Department of Neuroscience and Pharmacology, University of Copenhagen & Mental Health Centre Copenhagen, Rigshospitalet O-6102, 9 Blegdamsvej, DK-2100 Copenhagen, Denmark. Tel.: +45 3545 6113; Fax: +45 3539 3546; E-mail: pkoefoed@sund.ku.dk
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Extract

Objective: There is clear evidence of a genetic component in major depression, and several studies indicate that neuropeptide Y (NPY) could play an important role in the pathophysiology of the disease. A well-known polymorphism encoding the substitution of leucine to proline in the signal peptide sequence of NPY (Leu7Pro variation) was previously found to protect against depression. Our study aimed at replicating this association in a large Danish population with major depression.

Method: Leu7Pro was studied in a sample of depressed patients and ethnically matched controls, as well as psychiatric disease controls with schizophrenia. Possible functional consequences of Leu7Pro were explored in vitro.

Results: In contrast to previous studies, Pro7 appeared to be a risk allele for depression, being significantly more frequent in the depression sample (5.5%, n = 593; p = 0.009; odds ratio, OR: 1.46) as compared to ethnically matched controls (3.8%, n = 2912), while schizophrenia patients (4.1%, n = 503) did not differ. In vitro, the Pro7 substitution appeared to be associated with reduced levels of NPY without affecting its mRNA level.

Conclusion: The Leu7Pro variation may increase the risk of major depression, possibly by affecting the biosynthesis of NPY.

Keywords

candidate gene approachcase-control association studyNPY Leu7Promajor depression
Type
Research Article
Information
Acta Neuropsychiatrica , Volume 24 , Issue 2 , April 2012 , pp. 81 - 90
Copyright
Copyright © Cambridge University Press 2011

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