Ataxin-2 intermediate-length polyglutamine expansions in European ALS patients

作者：Lee Teresa; Li Yun R; Ingre Caroline; Weber Markus; Grehl Torsten; Gredal Ole; de Carvalho Mamede; Meyer Thomas; Tysnes Ole Bjorn; Auburger Georg; Gispert Suzana; Bonini Nancy M; Andersen Peter M; Gitler Aaron D^*

来源：Human Molecular Genetics, 2011, 20(9): 1697-1700.

DOI：10.1093/hmg/ddr045

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 x 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.

• 出版日期2011-5