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

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journal contribution
posted on 2014-03-21, 15:19 authored by Angelica Vittori, Michael Orth, Raymund A. C. Roos, Tiago F. Outeiro, Flaviano Giorgini, Edward J. Hollox, REGISTRY investigators of the European Huntington’s Disease Network
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.

Funding

AV is supported by Fundação para Ciência e a Tecnologia (SFRH/BD/4764/2008). TFO was supported by an EMBO Installation Grant and a Marie Curie International Reintegration Grant (Neurofold). FGwas supported by a New Investigator Research Grant from the Medical Research Council (G0700090). EJH was supported by a New Investigator Research Grant from the Medical Research Council (GO801123).

History

Citation

Journal of Huntington's Disease, 2013, 2 (1), pp. 107-124

Author affiliation

/Organisation/COLLEGE OF MEDICINE, BIOLOGICAL SCIENCES AND PSYCHOLOGY/School of Biological Sciences/Department of Genetics

Version

  • VoR (Version of Record)

Published in

Journal of Huntington's Disease

Publisher

IOS Press

issn

1879-6397

eissn

1879-6400

Copyright date

2013

Available date

2014-03-21

Publisher version

http://iospress.metapress.com/content/p2271460602l7333/

Language

en

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