title: β-Defensin Genomic Copy Number Does Not Influence the Age of Onset in Huntington's Disease.
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 byDEFB4- is an antimicrobial peptide that exhibits inducible expression in astrocytes during inflammation and is an important regulator of innate and adaptive immune response. Therefore,DEFB4may 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, includingDEFB4, modifies the AO in HD.
  
  
  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 thatDEFB4plays a role in HD pathogenesis.
authors.affiliation: Department of Genetics, University of Leicester, Leicester, UK ; Cell and Molecular Neuroscience Unit, Instituto de Medicina Molecular, Lisboa, Portugal.
authors.forename: Angelica
authors.initials: A
authors.lastname: Vittori
authors.affiliation: Department of Neurology, University of Ulm, Ulm, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Orth
authors.affiliation: Leiden University Medical Center, Department of Neurology, The Netherlands.
authors.forename: Raymund A C
authors.initials: RA
authors.lastname: Roos
authors.affiliation: Cell and Molecular Neuroscience Unit, Instituto de Medicina Molecular, Lisboa, Portugal ; Faculdade de Medicina da Universidade de Lisboa, Instituto de Fisiologia, Lisboa, Portugal ; University Medical Center Göttingen, Department of NeuroDegeneration and Restorative Research, Göttingen, Germany.
authors.forename: Tiago F
authors.initials: TF
authors.lastname: Outeiro
authors.affiliation: Department of Genetics, University of Leicester, Leicester, UK.
authors.forename: Flaviano
authors.initials: F
authors.lastname: Giorgini
authors.affiliation: Department of Genetics, University of Leicester, Leicester, UK.
authors.forename: Edward J
authors.initials: EJ
authors.lastname: Hollox
keywords: Genetic modifier; copy number variation; inflammation