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

Publication: Research - peer-reviewJournal article

Pernille Koefoed, David Paul Drucker Woldbye, Thomas v.O Hansen, Lene F Eplov, Søren Hofman Oliveira Christiansen, Ole Mors, Lars Vedel Kessing, Thomas Werge, Katja Kaipio, Ullamani Pesonen, Thomas Fahmy, Erling Thyge Mellerup, Klaus D Jakobsen, Elsebeth S Hansen, Gitte Moos Knudsen, Jens D Bukh, Camilla Bock, Camilla Lindberg, Ann S Kristensen, Henrik Dam & 6 others Merete Nordentoft, Thomas D Als, August G. Wang, Ulrik Gether, Jens Frederik Rehfeld, Tom Gert Bolwig

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.
Pernille
Original languageEnglish
JournalActa Neuropsychiatrica
Volume24
Issue number2
Pages (from-to)81-90
Number of pages10
ISSN0924-2708
DOIs
StatePublished - 23 Mar 2012

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