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

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; Merete Nordentoft; Thomas D Als; August G. Wang; Ulrik Gether; Jens Frederik Rehfeld; Tom Gert 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 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 DamMerete Nordentoft, Thomas D Als, August G. Wang, Ulrik Gether, Jens Frederik Rehfeld, Tom Gert Bolwig

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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.

Originalsprog	Engelsk
Tidsskrift	Acta Neuropsychiatrica
Vol/bind	24
Udgave nummer	2
Sider (fra-til)	81-90
Antal sider	10
ISSN	0924-2708
DOI	https://doi.org/10.1111/j.1601-5215.2011.00600.x
Status	Udgivet - apr. 2012

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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 depressionIndsendt manuskript, 580 KB

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Koefoed, P., Woldbye, D. P. D., Hansen, T. V. O., Eplov, L. F., Christiansen, S. H. O., Mors, O., Kessing, L. V., Werge, T., Kaipio, K., Pesonen, U., Fahmy, T., Mellerup, E. T., Jakobsen, K. D., Hansen, E. S., Knudsen, G. M., Bukh, J. D., Bock, C., Lindberg, C., Kristensen, A. S., ... Bolwig, T. G. (2012). 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

Koefoed, P, Woldbye, DPD, Hansen, TVO, Eplov, LF, Christiansen, SHO, Mors, O, Kessing, LV , Werge, T, Kaipio, K, Pesonen, U, Fahmy, T, Mellerup, ET, 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 2012, 'Association of the leucine-7 to proline-7 variation in the signal sequence of neuropeptide Y with major depression', Acta Neuropsychiatrica, bind 24, nr. 2, s. 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.",

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

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language = "English",

volume = "24",

pages = "81--90",

journal = "Acta Neuropsychiatrica",

issn = "0924-2708",

publisher = "Cambridge University Press",

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TY - JOUR

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

AU - Koefoed, Pernille

AU - Woldbye, David Paul Drucker

AU - Hansen, Thomas v.O

AU - Eplov, Lene F

AU - Christiansen, Søren Hofman Oliveira

AU - Mors, Ole

AU - Kessing, Lars Vedel

AU - Werge, Thomas

AU - Kaipio, Katja

AU - Pesonen, Ullamani

AU - Fahmy, Thomas

AU - Mellerup, Erling Thyge

AU - Jakobsen, Klaus D

AU - Hansen, Elsebeth S

AU - Knudsen, Gitte Moos

AU - Bukh, Jens D

AU - Bock, Camilla

AU - Lindberg, Camilla

AU - Kristensen, Ann S

AU - Dam, Henrik

AU - Nordentoft, Merete

AU - Als, Thomas D

AU - Wang, August G.

AU - Gether, Ulrik

AU - Rehfeld, Jens Frederik

AU - Bolwig, Tom Gert

PY - 2012/4

Y1 - 2012/4

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.

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

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