β-defensin genomic copy number does not influence the age of onset in huntington’s disease

REGISTRY investigators of the European Huntington’s Disease Network

doi:10.3233/JHD-130047

β-defensin genomic copy number does not influence the age of onset in huntington’s disease

REGISTRY investigators of the European Huntington’s Disease Network

University of Leicester
Instituto Gulbenkian de Medicina Molecular
Ulm University
University of Hamburg
Leiden University
University of Lisbon
University of Göttingen
National Research Council of Italy
University Hospital
University of Bern
University of Oslo
University of Copenhagen
Institut de Pathologie et de Génétique Gosselies
Institute of Psychiatry and Neurology, Warszawa
IRCCS Fondazione Istituto Neurologico Carlo Besta - Milano
Cardiff & Vale University Health Board
Sheffield Teaching Hospitals NHS Foundation Trust
University of Medical Sciences Poznan
Centrum extrapyramidových onemocnĕní
Rehabilitation Centre Suvituuli
Terveystalo Healthcare
RWTH Aachen University
Ruhr University Bochum
Reha Zentrum in Dinslaken im Gesundheitszentrums Lang
University of Münster
Technische Universität Dresden
University of Freiburg
Psychatrium Heiligenhafen
Neurologie und Psychiatrie
Klinik für Psychiatrie und Psychotherapie
Technical University of Munich
Klinik Taufkirchen (Vils)
University of Bari
University of Florence
University of Genoa
Federico II University Hospital
IRCCS Istituto Neurologico Mediterraneo Neuromed - Pozzilli (IS)
Medisch Spectrum Twente
Polikliniek Neurologie
Radboud University Nijmegen
Dept. of Medical Genetics
Norwegian University of Science and Technology
St. Adalbert Hospital
Medical University of Silesia in Katowice
Krakowska Akademia Neurologii
Medical University of Warsaw
Hospital São João E.P.E.
Hospital Virgen de los Lirios
Hospital Universitario Infanta Cristina
Hospital Universitario de Burgos
Hospital Universitario San Cecilio
Hospital Universitario de Fuenlabrada
Hospital Clínico San Carlos de Madrid
Hospital Ramon y Cajal
Fundación Jiménez Díaz
Hospital Virgen de la Arrixaca
Barcelona-Hospital Mútua de Terrassa
Hospital Universitari de Bellvitge
IDIBAPS
Hospital Mare de Deu de La Merced
Karolinska Institutet
Neurologische Klinik und Poliklinik
Birmingham and Solihull Mental Health NHS Foundation Trust
University of Cambridge
University of Manchester
NHS Lothian
NHS Fife
Gloucestershire Hospitals NHS Foundation Trust
Leeds Teaching Hospitals NHS Trust
Leicestershire Partnership Trust
Guy's and St Thomas' NHS Foundation Trust
University College London Hospitals NHS Foundation Trust
Oxford University Hospitals NHS Foundation Trust
Mount Gould Hospital

Research output: Contribution to journal › Article › peer-review

1 Scopus citations

Abstract

Background: Huntington’s disease (HD) is an autosomal dominant neurodegenerative disorder caused by the abnormal expansion of a CAG triplet repeat tract in the huntingtin gene. While the length of this CAG expansion is the major determinant of the age of onset (AO), other genetic factors have also been shown to play a modulatory role. Recent evidence suggests that neuroinflammation is a pivotal factor in the pathogenesis of HD, and that targeting this process may have important therapeutic ramifications. The human β-defensin 2 (hBD2) - encoded by DEFB4 - is an antimicrobial peptide that exhibits inducible expression in astrocytes during inflammation and is an important regulator of innate and adaptive immune response. Therefore, DEFB4 may contribute to the neuroinflammatory processes observed in HD. Objective: In this study we tested the hypothesis that copy number variation (CNV) of the β-defensin region, including DEFB4, modifies the AO in HD. Methods and results: We genotyped β-defensin CNV in 490 HD individuals using the paralogue ratio test and found no association between β-defensin CNV and onset of HD. Conclusions: We conclude that it is unlikely that DEFB4 plays a role in HD pathogenesis.

Original language	English
Pages (from-to)	107-124
Number of pages	18
Journal	Journal of Huntington's disease
Volume	2
Issue number	1
DOIs	https://doi.org/10.3233/JHD-130047
State	Published - 1 Jan 2013
Externally published	Yes

Funding

Funders	Funder number
Medical Research Council	G0801123, G0700090

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

Copy number variation
Genetic modifier
Inflammation

Access to Document

10.3233/JHD-130047

Cite this

@article{d88a24ebe407450cb757e594da905165,

title = "β-defensin genomic copy number does not influence the age of onset in huntington{\textquoteright}s disease",

abstract = "Background: Huntington{\textquoteright}s disease (HD) is an autosomal dominant neurodegenerative disorder caused by the abnormal expansion of a CAG triplet repeat tract in the huntingtin gene. While the length of this CAG expansion is the major determinant of the age of onset (AO), other genetic factors have also been shown to play a modulatory role. Recent evidence suggests that neuroinflammation is a pivotal factor in the pathogenesis of HD, and that targeting this process may have important therapeutic ramifications. The human β-defensin 2 (hBD2) - encoded by DEFB4 - is an antimicrobial peptide that exhibits inducible expression in astrocytes during inflammation and is an important regulator of innate and adaptive immune response. Therefore, DEFB4 may contribute to the neuroinflammatory processes observed in HD. Objective: In this study we tested the hypothesis that copy number variation (CNV) of the β-defensin region, including DEFB4, modifies the AO in HD. Methods and results: We genotyped β-defensin CNV in 490 HD individuals using the paralogue ratio test and found no association between β-defensin CNV and onset of HD. Conclusions: We conclude that it is unlikely that DEFB4 plays a role in HD pathogenesis.",

keywords = "Copy number variation, Genetic modifier, Inflammation",

author = "\{REGISTRY investigators of the European Huntington{\textquoteright}s Disease Network\} and Angelica Vittori and Michael Orth and Roos, \{Raymund A.C.\} and Outeiro, \{Tiago F.\} and Flaviano Giorgini and Hollox, \{Edward J.\} and Bachoud-L{\'e}vi, \{A. C.\} and Bentivoglio, \{Anna Rita\} and I. Biunno and Bonelli, \{Raphael M.\} and Burgunder, \{Jean Marc\} and Dunnett, \{S. B.\} and Ferreira, \{Joaquim J.\} and Arvid Heiberg and T. Illmann and Landwehrmeyer, \{G. B.\} and J. Levey and Martinez-Jaurrieta, \{M. D.\} and Nielsen, \{J{\o}rgen E.\} and \{Pro Koivisto\}, S. and M. P{\"a}iv{\"a}rinta and \{Rojo Sebasti{\'a}n\}, A. and Tabrizi, \{S. J.\} and W. Vandenberghe and Christine Verellen-Dumoulin and Jacek Zaremba and T. Uhrova and J. Wahlstr{\"o}m and Katrin Barth and Leonor Correia-Guedes and Finisterra, \{A. M.\} and \{Bascu{\~n}ana Garde\}, M. and S. Betz and Reineke Bos and Daniel Ecker and Handley, \{O. J.\} and Christine Held and K. Koppers and M. Laur{\'a} and \{Mart{\'i}nez Descals\}, A. and Tiago Mestre and Daniela Monza and Jenny Townhill and H. Padieu and L. Paterski and Nadia Peppa and A. Rialland and N. R{\o}ren and P. Sasinkov{\'a} and Sara Minster",

year = "2013",

month = jan,

day = "1",

doi = "10.3233/JHD-130047",

language = "אנגלית",

volume = "2",

pages = "107--124",

journal = "Journal of Huntington's disease",

issn = "1879-6397",

publisher = "SAGE Publications Ltd",

number = "1",

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TY - JOUR

T1 - β-defensin genomic copy number does not influence the age of onset in huntington’s disease

AU - REGISTRY investigators of the European Huntington’s Disease Network

AU - Vittori, Angelica

AU - Orth, Michael

AU - Roos, Raymund A.C.

AU - Outeiro, Tiago F.

AU - Giorgini, Flaviano

AU - Hollox, Edward J.

AU - Bachoud-Lévi, A. C.

AU - Bentivoglio, Anna Rita

AU - Biunno, I.

AU - Bonelli, Raphael M.

AU - Burgunder, Jean Marc

AU - Dunnett, S. B.

AU - Ferreira, Joaquim J.

AU - Heiberg, Arvid

AU - Illmann, T.

AU - Landwehrmeyer, G. B.

AU - Levey, J.

AU - Martinez-Jaurrieta, M. D.

AU - Nielsen, Jørgen E.

AU - Pro Koivisto, S.

AU - Päivärinta, M.

AU - Rojo Sebastián, A.

AU - Tabrizi, S. J.

AU - Vandenberghe, W.

AU - Verellen-Dumoulin, Christine

AU - Zaremba, Jacek

AU - Uhrova, T.

AU - Wahlström, J.

AU - Barth, Katrin

AU - Correia-Guedes, Leonor

AU - Finisterra, A. M.

AU - Bascuñana Garde, M.

AU - Betz, S.

AU - Bos, Reineke

AU - Ecker, Daniel

AU - Handley, O. J.

AU - Held, Christine

AU - Koppers, K.

AU - Laurá, M.

AU - Martínez Descals, A.

AU - Mestre, Tiago

AU - Monza, Daniela

AU - Townhill, Jenny

AU - Padieu, H.

AU - Paterski, L.

AU - Peppa, Nadia

AU - Rialland, A.

AU - Røren, N.

AU - Sasinková, P.

AU - Minster, Sara

PY - 2013/1/1

Y1 - 2013/1/1

N2 - Background: Huntington’s disease (HD) is an autosomal dominant neurodegenerative disorder caused by the abnormal expansion of a CAG triplet repeat tract in the huntingtin gene. While the length of this CAG expansion is the major determinant of the age of onset (AO), other genetic factors have also been shown to play a modulatory role. Recent evidence suggests that neuroinflammation is a pivotal factor in the pathogenesis of HD, and that targeting this process may have important therapeutic ramifications. The human β-defensin 2 (hBD2) - encoded by DEFB4 - is an antimicrobial peptide that exhibits inducible expression in astrocytes during inflammation and is an important regulator of innate and adaptive immune response. Therefore, DEFB4 may contribute to the neuroinflammatory processes observed in HD. Objective: In this study we tested the hypothesis that copy number variation (CNV) of the β-defensin region, including DEFB4, modifies the AO in HD. Methods and results: We genotyped β-defensin CNV in 490 HD individuals using the paralogue ratio test and found no association between β-defensin CNV and onset of HD. Conclusions: We conclude that it is unlikely that DEFB4 plays a role in HD pathogenesis.

AB - Background: Huntington’s disease (HD) is an autosomal dominant neurodegenerative disorder caused by the abnormal expansion of a CAG triplet repeat tract in the huntingtin gene. While the length of this CAG expansion is the major determinant of the age of onset (AO), other genetic factors have also been shown to play a modulatory role. Recent evidence suggests that neuroinflammation is a pivotal factor in the pathogenesis of HD, and that targeting this process may have important therapeutic ramifications. The human β-defensin 2 (hBD2) - encoded by DEFB4 - is an antimicrobial peptide that exhibits inducible expression in astrocytes during inflammation and is an important regulator of innate and adaptive immune response. Therefore, DEFB4 may contribute to the neuroinflammatory processes observed in HD. Objective: In this study we tested the hypothesis that copy number variation (CNV) of the β-defensin region, including DEFB4, modifies the AO in HD. Methods and results: We genotyped β-defensin CNV in 490 HD individuals using the paralogue ratio test and found no association between β-defensin CNV and onset of HD. Conclusions: We conclude that it is unlikely that DEFB4 plays a role in HD pathogenesis.

KW - Copy number variation

KW - Genetic modifier

KW - Inflammation

UR - https://www.scopus.com/pages/publications/84906932590

U2 - 10.3233/JHD-130047

DO - 10.3233/JHD-130047

M3 - ???researchoutput.researchoutputtypes.contributiontojournal.article???

C2 - 25057107

AN - SCOPUS:84906932590

SN - 1879-6397

VL - 2

SP - 107

EP - 124

JO - Journal of Huntington's disease

JF - Journal of Huntington's disease

IS - 1

ER -

β-defensin genomic copy number does not influence the age of onset in huntington’s disease

Abstract

Funding

UN SDGs

Keywords

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