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

Pernille Kofoed, David P.D. Woldbye, Thomas v O. Hansen, Lene F. Eplov, Søren H. Christiansen, Ole Mors, Lars V. Kessing, Thomas Werge, Katja Kaipio, Ullamari Pesonen, Thomas Fahmy, Erling Mellerup, Klaus D. Jakobsen, Elsebeth S. Hansen, Gitte M. Knudsen, Jens D. Bukh, Camilla Bock, Camilla Lindberg, Ann S. Kristensen, Henrik DamMerete Nordentoft, Thomas Damm Als, August G. Wang, Ulrik Gether, Jens F. Rehfeld, Tom G. Bolwig

Research output: Contribution to journalJournal articleResearchpeer-review

Abstract

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
Volume24
Issue number2
Pages (from-to)81–90
ISSN0924-2708
DOIs
Publication statusPublished - 2011
Externally publishedYes

Keywords

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

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