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

Publication: Research - peer-reviewJournal article – Annual report year: 2011

Without internal affiliation

  • Author: Kofoed, Pernille

    University of Copenhagen2, Denmark

  • Author: Woldbye, David P.D.

    University of Copenhagen2, Denmark

  • Author: Hansen, Thomas v O.

    University of Copenhagen2, Denmark

  • Author: Eplov, Lene F.

    Copenhagen University Hospital, Denmark

  • Author: Christiansen, Søren H.

    University of Copenhagen2, Denmark

  • Author: Mors, Ole

    Aarhus University Hospital, Denmark

  • Author: Kessing, Lars V.

    Copenhagen University Hospital, Denmark

  • Author: Werge, Thomas

    St Hans Hospital Roskilde, Research Institute of Biological Psychiatry, Denmark

  • Author: Kaipio, Katja

    University of Turku, Finland

  • Author: Pesonen, Ullamari

    University of Turku, Finland

  • Author: Fahmy, Thomas

    Copenhagen University Hospital, Denmark

  • Author: Mellerup, Erling

    University of Copenhagen2, Denmark

  • Author: Jakobsen, Klaus D.

    St Hans Hospital Roskilde, Research Institute of Biological Psychiatry, Denmark

  • Author: Hansen, Elsebeth S.

    Copenhagen University Hospital, Denmark

  • Author: Knudsen, Gitte M.

    Copenhagen University Hospital, Denmark

  • Author: Bukh, Jens D.

    Copenhagen University Hospital, Denmark

  • Author: Bock, Camilla

    Copenhagen University Hospital, Denmark

  • Author: Lindberg, Camilla

    University of Copenhagen2, Denmark

  • Author: Kristensen, Ann S.

    Aarhus University Hospital, Denmark

  • Author: Dam, Henrik

    Copenhagen University Hospital, Denmark

  • Author: Nordentoft, Merete

  • Author: Als, Thomas Damm

    Aarhus University Hospital

  • Author: Wang, August G.

    Mental Health Centre Amager, Denmark

  • Author: Gether, Ulrik

    University of Copenhagen2, Denmark

  • Author: Rehfeld, Jens F.

    Copenhagen University Hospital, Denmark

  • Author: Bolwig, Tom G.

    University of Copenhagen2, Denmark

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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.
Original languageEnglish
JournalActa Neuropsychiatrica
Publication date2011
Volume24
Issue2
Pages81–90
ISSN0924-2708
DOIs
StatePublished
CitationsWeb of Science® Times Cited: 1

Keywords

  • Candidate gene approach, Case-control association study, NPY Leu7Pro, Major depression
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