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 Dam; Merete Nordentoft; Thomas Damm Als; August G. Wang; Ulrik Gether; Jens F. Rehfeld; Tom G. Bolwig

doi:10.1111/j.1601-5215.2011.00600.x

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 journal › Journal article › Research › peer-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 language	English
Journal	Acta Neuropsychiatrica
Volume	24
Issue number	2
Pages (from-to)	81–90
ISSN	0924-2708
DOIs	https://doi.org/10.1111/j.1601-5215.2011.00600.x
Publication status	Published - 2011
Externally published	Yes

Keywords

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

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Kofoed, P., Woldbye, D. P. D., Hansen, T. V. O., Eplov, L. F., Christiansen, S. H., Mors, O., Kessing, L. V., Werge, T., Kaipio, K., Pesonen, U., Fahmy, T., Mellerup, E., Jakobsen, K. D., Hansen, E. S., Knudsen, G. M., Bukh, J. D., Bock, C., Lindberg, C., Kristensen, A. S., ... Bolwig, T. G. (2011). Association of the leucine-7 to proline-7 variation in the signal sequence of neuropeptide Y with major depression. Acta Neuropsychiatrica, 24(2), 81–90. https://doi.org/10.1111/j.1601-5215.2011.00600.x

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

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.",

keywords = "Candidate gene approach, Case-control association study, NPY Leu7Pro, Major depression",

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

year = "2011",

doi = "10.1111/j.1601-5215.2011.00600.x",

language = "English",

volume = "24",

pages = "81–90",

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Kofoed, P, Woldbye, DPD, Hansen, TVO, Eplov, LF, Christiansen, SH, Mors, O, Kessing, LV, Werge, T, Kaipio, K, Pesonen, U, Fahmy, T, Mellerup, E, Jakobsen, KD, Hansen, ES, Knudsen, GM, Bukh, JD, Bock, C, Lindberg, C, Kristensen, AS, Dam, H, Nordentoft, M, Als, TD, Wang, AG, Gether, U, Rehfeld, JF & Bolwig, TG 2011, 'Association of the leucine-7 to proline-7 variation in the signal sequence of neuropeptide Y with major depression', Acta Neuropsychiatrica, vol. 24, no. 2, pp. 81–90. https://doi.org/10.1111/j.1601-5215.2011.00600.x

TY - JOUR

T1 - Association of the leucine-7 to proline-7 variation in the signal sequence of neuropeptide Y with major depression

AU - Kofoed, Pernille

AU - Woldbye, David P.D.

AU - Hansen, Thomas v O.

AU - Eplov, Lene F.

AU - Christiansen, Søren H.

AU - Mors, Ole

AU - Kessing, Lars V.

AU - Werge, Thomas

AU - Kaipio, Katja

AU - Pesonen, Ullamari

AU - Fahmy, Thomas

AU - Mellerup, Erling

AU - Jakobsen, Klaus D.

AU - Hansen, Elsebeth S.

AU - Knudsen, Gitte M.

AU - Bukh, Jens D.

AU - Bock, Camilla

AU - Lindberg, Camilla

AU - Kristensen, Ann S.

AU - Dam, Henrik

AU - Nordentoft, Merete

AU - Als, Thomas Damm

AU - Wang, August G.

AU - Gether, Ulrik

AU - Rehfeld, Jens F.

AU - Bolwig, Tom G.

PY - 2011

Y1 - 2011

N2 - 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.

AB - 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.

KW - Candidate gene approach

KW - Case-control association study

KW - NPY Leu7Pro

KW - Major depression

U2 - 10.1111/j.1601-5215.2011.00600.x

DO - 10.1111/j.1601-5215.2011.00600.x

M3 - Journal article

C2 - 26952950

SN - 0924-2708

VL - 24

SP - 81

EP - 90

JO - Acta Neuropsychiatrica

JF - Acta Neuropsychiatrica

IS - 2

ER -

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

Abstract

Keywords

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