Analysis of the KIFAP3 gene in amyotrophic lateral sclerosis: a multicenter survival study

Perry T C van Doormaal; Nicola Ticozzi; Cinzia Gellera; Antonia Ratti; Franco Taroni; Adriano Chiò; Andrea Calvo; Gabriele Mora; Gabriella Restagno; Bryan J Traynor; Anna Birve; Robin Lemmens; Michael A van Es; Christiaan G J Saris; Hylke M Blauw; Paul W J van Vught; Ewout J N Groen; Lucia Corrado; Letizia Mazzini; Roberto Del Bo; Stefania Corti; Stefan Waibel; Thomas Meyer; Albert C Ludolph; An Goris; Philip van Damme; Wim Robberecht; Aleksey Shatunov; Isabella Fogh; Peter M Andersen; Sandra D'Alfonso; Orla Hardiman; Simon Cronin; Dan Rujescu; Ammar Al-Chalabi; John E Landers; Vincenzo Silani; Leonard H van den Berg; Jan H Veldink

doi:10.1016/j.neurobiolaging.2014.04.014

Analysis of the KIFAP3 gene in amyotrophic lateral sclerosis: a multicenter survival study

Neurobiol Aging. 2014 Oct;35(10):2420.e13-4. doi: 10.1016/j.neurobiolaging.2014.04.014. Epub 2014 Apr 19.

Authors

Perry T C van Doormaal¹, Nicola Ticozzi², Cinzia Gellera³, Antonia Ratti², Franco Taroni³, Adriano Chiò⁴, Andrea Calvo⁴, Gabriele Mora⁵, Gabriella Restagno⁶, Bryan J Traynor⁷, Anna Birve⁸, Robin Lemmens⁹, Michael A van Es¹, Christiaan G J Saris¹, Hylke M Blauw¹, Paul W J van Vught¹, Ewout J N Groen¹, Lucia Corrado¹⁰, Letizia Mazzini¹¹, Roberto Del Bo¹², Stefania Corti¹², Stefan Waibel¹³, Thomas Meyer¹⁴, Albert C Ludolph¹³, An Goris¹⁵, Philip van Damme⁹, Wim Robberecht⁹, Aleksey Shatunov¹⁶, Isabella Fogh¹⁶, Peter M Andersen⁸, Sandra D'Alfonso¹⁰, Orla Hardiman¹⁷, Simon Cronin¹⁸, Dan Rujescu¹⁹, Ammar Al-Chalabi¹⁶, John E Landers²⁰, Vincenzo Silani², Leonard H van den Berg¹, Jan H Veldink²¹

Affiliations

¹ Department of Neurology, University Medical Center Utrecht, Rudolf Magnus Institute of Neuroscience, Utrecht, the Netherlands.
² Unit of Neurology and Laboratory of Neuroscience, IRCCS Istituto Auxologico Italiano, Milan, Italy; Department of Pathophysiology and Transplantation, "Dino Ferrari" Center, Università degli Studi di Milano, Milan, Italy.
³ Unit of Genetics of Neurodegenerative and Metabolic Diseases, IRCCS Carlo Besta Neurological Institute, Milan, Italy.
⁴ 'Rita Levi Montalcini' Department of Neuroscience, University of Turin, Turin, Italy.
⁵ ALS Center, Salvatore Maugeri Foundation, IRCSS, Milan, Italy.
⁶ Laboratory of Molecular Genetics, Città della Salute e della Scienza Hospital, Turin, Italy.
⁷ Neuromuscular Diseases Research Group, Laboratory of Neurogenetics, National Institute on Aging, Bethesda, MD, USA.
⁸ The Institute of Pharmacology and Clinical Neuroscience, Umeå University, Umeå, Sweden.
⁹ Leuven Institute for Neurodegenerative Disorders (LIND), University of Leuven, Leuven, Belgium; Vesalius Research Center Center (VRC), Flanders Institute for Biotechnology (VIB), Leuven, Belgium; Department of Clinical and Experimental Neurology, University Hospital Leuven, University of Leuven, Leuven, Belgium.
¹⁰ Department of Health Sciences and Interdisciplinary Research Center of Autoimmune Diseases (IRCAD), University of Eastern Piedmont, Novara, Italy.
¹¹ Department of Neurology, A. Avogadro University and Maggiore della Carità Hospital, Novara, Italy.
¹² Department of Pathophysiology and Transplantation, "Dino Ferrari" Center, Università degli Studi di Milano, Milan, Italy; Neurologic Unit, IRCCS Foundation Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.
¹³ Department of Neurology, University of Ulm, Ulm, Germany.
¹⁴ Department of Neurology, Charité University Hospital, Humboldt-University, Berlin, Germany.
¹⁵ Leuven Institute for Neurodegenerative Disorders (LIND), University of Leuven, Leuven, Belgium; Laboratory for Neuroimmunology, Section for Experimental Neurology, KU Leuven, Leuven, Belgium.
¹⁶ Department of Clinical Neuroscience, King's College London, Institute of Psychiatry, London, UK.
¹⁷ Trinity College Institute of Neurosciences, Trinity College, Dublin, Ireland; Department of Neurology, Beaumont Hospital, Dublin, Ireland.
¹⁸ Department of Neurology, Beaumont Hospital, Dublin, Ireland; Department of Clinical Neurological Sciences, Royal College of Surgeons in Ireland, Dublin, Ireland.
¹⁹ Department of Psychiatry, University of Halle, Halle, Germany.
²⁰ Department of Neurology, University of Massachusetts Medical School, Worcester, MA, USA.
²¹ Department of Neurology, University Medical Center Utrecht, Rudolf Magnus Institute of Neuroscience, Utrecht, the Netherlands. Electronic address: j.h.veldink@umcutrecht.nl.

PMID: 24838185
PMCID: PMC5496711
DOI: 10.1016/j.neurobiolaging.2014.04.014

Abstract

Sporadic amyotrophic lateral sclerosis is a multifactorial disease of environmental and genetic origin. In a previous large multicenter genome wide study, common genetic variation in the Kinesin-Associated Protein 3 (KIFAP3) gene (rs1541160) was reported to have a significant effect on survival in amyotrophic lateral sclerosis patients. However, this could not be replicated in 3 smaller independent cohorts. We conducted a large multicenter multivariate survival analysis (n = 2362) on the effect of genetic variation in rs1541160. The previously reported beneficial genotype did not show a significant improvement in survival in this patient group.

Keywords: Amyotrophic lateral sclerosis; Genome-wide association study; KIFAP3; Kinesin-associated protein 3 gene.

Publication types

Multicenter Study

MeSH terms

Adaptor Proteins, Signal Transducing / genetics*
Aged
Amyotrophic Lateral Sclerosis / genetics*
Amyotrophic Lateral Sclerosis / mortality*
Cohort Studies
Cytoskeletal Proteins / genetics*
Female
Genetic Variation / genetics*
Genome-Wide Association Study*
Genotype
Humans
Male
Middle Aged
Polymorphism, Single Nucleotide
Survival Analysis

Substances

Adaptor Proteins, Signal Transducing
Cytoskeletal Proteins
KIFAP3 protein, human

Abstract

Publication types

MeSH terms

Substances

Grants and funding