ATXN2 trinucleotide repeat length correlates with risk of ALS.
Neurobiology of Aging. 2017-03-01; 51: 178.e1-178.e9
DOI: 10.1016/j.neurobiolaging.2016.11.010
Read on PubMed
1. Neurobiol Aging. 2017 Mar;51:178.e1-178.e9. doi:
10.1016/j.neurobiolaging.2016.11.010. Epub 2016 Nov 24.
ATXN2 trinucleotide repeat length correlates with risk of ALS.
Sproviero W(1), Shatunov A(1), Stahl D(2), Shoai M(3), van Rheenen W(4), Jones
AR(1), Al-Sarraj S(5), Andersen PM(6), Bonini NM(7), Conforti FL(8), Van Damme
P(9), Daoud H(10), Del Mar Amador M(11), Fogh I(1), Forzan M(12), Gaastra B(1),
Gellera C(13), Gitler AD(14), Hardy J(3), Fratta P(15), La Bella V(16), Le Ber
I(17), Van Langenhove T(18), Lattante S(19), Lee YC(20), Malaspina A(21),
Meininger V(22), Millecamps S(19), Orrell R(23), Rademakers R(24), Robberecht
W(25), Rouleau G(10), Ross OA(24), Salachas F(26), Sidle K(3), Smith BN(1), Soong
BW(20), Sorarù G(27), Stevanin G(28), Kabashi E(19), Troakes C(1), van
Broeckhoven C(29), Veldink JH(4), van den Berg LH(4), Shaw CE(1), Powell JF(1),
Al-Chalabi A(30).
Author information:
(1)Department of Basic and Clinical Neuroscience, King’s College London, Maurice
Wohl Clinical Neuroscience Institute, London, UK.
(2)Department of Biostatistics, King’s College London, Institute of Psychiatry,
Psychology and Neuroscience, London, UK.
(3)Department of Molecular Neuroscience, University College London (UCL)
Institute of Neurology, London, UK.
(4)Department of Neurology, Brain Center Rudolf Magnus Institute of Neuroscience,
University Medical Centre Utrecht, Utrecht, the Netherlands.
(5)Department of Clinical Neuropathology, King’s College Hospital NHS Foundation
Trust, London, UK.
(6)Department of Pharmacology and Clinical Neuroscience, Umeå University, Umeå,
Sweden.
(7)Department of Biology, University of Pennsylvania, Philadelphia, PA, USA.
(8)Institute of Neurological Sciences, National Research Council, Cosenza, Italy.
(9)Neurology Department, University Hospitals Leuven, Leuven, Belgium; Vesalius
Research Center, VIB, Leuven, Belgium; Disease (LIND), KU Leuven – University of
Leuven, Leuven, Belgium.
(10)Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada.
(11)Department of Nervous System Diseases, ALS Paris ALS Center for Rare
Diseases, Groupe Hospitalier Pitié Salpêtrière, APHP, Paris, France.
(12)Clinical Genetics Unit, Department of Woman and Child Health, University of
Padova, Padova, Italy.
(13)Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy.
(14)Department of Genetics, Stanford University School of Medicine, Stanford, CA,
USA.
(15)Sobell Department of Motor Neuroscience and Movement Disorders, University
College London (UCL) Institute of Neurology, London, UK.
(16)ALS Clinical Research Center, Bio. Ne. C., University of Palermo, Palermo,
Italy.
(17)Institut du Cerveau et de la Moelle épinière (ICM), Inserm U1127, CNRS UMR
7225, Sorbonne Universités, UPMC Univ Paris 06 UMRS1127, Paris, France; AP-HP,
Hôpitaux Universitaires La Pitié Salpêtrière-Charles Foix, Centre de Référence
des Démences Rares, Departement de Neurologie, Paris, France.
(18)Neurodegenerative Brain Diseases Group, Department of Molecular Genetics,
VIB, Antwerp, Belgium; Laboratory of Neurogenetics, Insititute Born-Bunge,
University of Antwerp, Antwerp, Belgium; Department of Neurology, Antwerp
University Hospital, Edegem, Belgium.
(19)Institut du Cerveau et de la Moelle épinière (ICM), Inserm U1127, CNRS UMR
7225, Sorbonne Universités, UPMC Univ Paris 06 UMRS1127, Paris, France.
(20)Department of Neurology, Taipei Veterans General Hospital, Taipei, Taiwan;
Department of Neurology, National Yang-Ming University School of Medicine,
Taipei, Taiwan; Brain Research Center, National Yang-Ming University, Taipei,
Taiwan.
(21)North-East London and Essex MND Care Centre – Neuroscience and Trauma Centre,
Blizard, Institute of Cell and Molecular Medicine, Barts & the London School of
Medicine & Dentistry, Barts Health NHS Trust, London, UK.
(22)Hôpital de la Pitié-Salpêtrière, institut de recherche translationnelle en
neurosciences (A-ICM), Paris, France; Hôpital de la Pitié-Salpêtrière, réseau SLA
IdF, Paris, France.
(23)Department of Clinical Neuroscience, University College London (UCL)
Institute of Neurology, London, UK.
(24)Department of Neuroscience, Mayo Clinic, Jacksonville, FL, USA.
(25)Vesalius Research Center, VIB, Leuven, Belgium; Disease (LIND), KU Leuven –
University of Leuven, Leuven, Belgium.
(26)Department of Nervous System Diseases, ALS Paris ALS Center for Rare
Diseases, Groupe Hospitalier Pitié Salpêtrière, APHP, Paris, France; Institut du
Cerveau et de la Moelle épinière (ICM), Inserm U1127, CNRS UMR 7225, Sorbonne
Universités, UPMC Univ Paris 06 UMRS1127, Paris, France.
(27)Department of Neurosciences, University of Padova, Padova, Italy.
(28)Institut du Cerveau et de la Moelle épinière (ICM), Inserm U1127, CNRS UMR
7225, Sorbonne Universités, UPMC Univ Paris 06 UMRS1127, Paris, France;
Neurogenetics team, Ecole Pratique des Hautes Etudes, Paris, France.
(29)Neurodegenerative Brain Diseases Group, Department of Molecular Genetics,
VIB, Antwerp, Belgium; Laboratory of Neurogenetics, Insititute Born-Bunge,
University of Antwerp, Antwerp, Belgium.
(30)Department of Basic and Clinical Neuroscience, King’s College London, Maurice
Wohl Clinical Neuroscience Institute, London, UK. Electronic address:
.
We investigated a CAG trinucleotide repeat expansion in the ATXN2 gene in
amyotrophic lateral sclerosis (ALS). Two new case-control studies, a British
dataset of 1474 ALS cases and 567 controls, and a Dutch dataset of 1328 ALS cases
and 691 controls were analyzed. In addition, to increase power, we systematically
searched PubMed for case-control studies published after 1 August 2010 that
investigated the association between ATXN2 intermediate repeats and ALS. We
conducted a meta-analysis of the new and existing studies for the relative risks
of ATXN2 intermediate repeat alleles of between 24 and 34 CAG trinucleotide
repeats and ALS. There was an overall increased risk of ALS for those carrying
intermediate sized trinucleotide repeat alleles (odds ratio 3.06 [95% confidence
interval 2.37-3.94]; p = 6 × 10-18), with an exponential relationship between
repeat length and ALS risk for alleles of 29-32 repeats (R2 = 0.91, p = 0.0002).
No relationship was seen for repeat length and age of onset or survival. In
contrast to trinucleotide repeat diseases, intermediate ATXN2 trinucleotide
repeat expansion in ALS does not predict age of onset but does predict disease
risk.
Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.
DOI: 10.1016/j.neurobiolaging.2016.11.010
PMCID: PMC5302215 [Available on 2017-03-01]
PMID: 28017481 [Indexed for MEDLINE]