title: Ataxin-2 intermediate-length polyglutamine expansions in European ALS patients.
abstract: Amyotrophic lateral sclerosis (ALS) is a fatal adult-onset neurodegenerative disease primarily affecting motor neurons. We recently identified intermediate-length polyglutamine (polyQ) expansions (27-33 Qs) in ataxin 2 as a genetic risk factor for sporadic ALS in North American ALS patients. To extend these findings, we assessed the ataxin 2 polyQ repeat length in 1294 European ALS patients and 679 matched healthy controls. We observed a significant association between polyQ expansions and ALS (>30 Qs; P= 6.2 × 10(-3)). Thus, intermediate-length ataxin 2 polyQ repeat expansions are associated with increased risk for ALS also in the European cohort. The specific polyQ length cutoff, however, appears to vary between different populations, with longer repeat lengths showing a clear association. Our findings support the hypothesis that ataxin 2 plays an important role in predisposing to ALS and that polyQ expansions in ataxin 2 are a significant risk factor for the disease.
authors.affiliation: Department of Cell and Developmental Biology, the University of Pennsylvania School of Medicine, 1109 BRB II/III, 421 Curie Blvd., Philadelphia, PA 19104, USA.
authors.forename: Teresa
authors.initials: T
authors.lastname: Lee
authors.forename: Yun R
authors.initials: YR
authors.lastname: Li
authors.forename: Caroline
authors.initials: C
authors.lastname: Ingre
authors.forename: Markus
authors.initials: M
authors.lastname: Weber
authors.forename: Torsten
authors.initials: T
authors.lastname: Grehl
authors.forename: Ole
authors.initials: O
authors.lastname: Gredal
authors.forename: Mamede
authors.initials: M
authors.lastname: de Carvalho
authors.forename: Thomas
authors.initials: T
authors.lastname: Meyer
authors.forename: Ole-Björn
authors.initials: OB
authors.lastname: Tysnes
authors.forename: Georg
authors.initials: G
authors.lastname: Auburger
authors.forename: Suzana
authors.initials: S
authors.lastname: Gispert
authors.forename: Nancy M
authors.initials: NM
authors.lastname: Bonini
authors.forename: Peter M
authors.initials: PM
authors.lastname: Andersen
authors.forename: Aaron D
authors.initials: AD
authors.lastname: Gitler
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics* / Q000378:metabolism*; D000067528:Ataxins; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000378:metabolism; D010455:Peptides / Q000378:metabolism*; D012307:Risk Factors; D019680:Trinucleotide Repeat Expansion; D044465:White People / Q000235:genetics*
chemical_list: D000067528:Ataxins; D009419:Nerve Tissue Proteins; D010455:Peptides; C097188:polyglutamine