Association of long ATXN2 CAG repeat sizes with increased risk of amyotrophic lateral sclerosis

Arch Neurol. 2011 Jun;68(6):739-42. doi: 10.1001/archneurol.2011.111.

Abstract

Objective: To analyze the ataxin 2 (ATXN2) CAG repeat size in a cohort of patients with amyotrophic lateral sclerosis (ALS) and healthy controls. Large (CAG)(n) alleles of the ATXN2 gene (27-33 repeats) were recently reported to be associated with an increased risk of ALS.

Design: Case-control study.

Setting: France and Quebec, Canada.

Participants: A total of 556 case patients with ALS and 471 healthy controls; both groups of participants are of French or French-Canadian origin.

Results: We observed a significant association between ATXN2 high-length alleles (≥29 CAG repeats) and ALS in French and French-Canadian ALS populations. Furthermore, we identified spinocerebellar ataxia type 2-pathogenic polyglutamine expansions (≥32 CAG repeats) in both familial and sporadic ALS cases.

Conclusions: Altogether, our findings support ATXN2 high-length repeats as a risk factor for ALS and further indicate a genetic link between spinocerebellar ataxia type 2 and ALS.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Amyotrophic Lateral Sclerosis / epidemiology
  • Amyotrophic Lateral Sclerosis / ethnology
  • Amyotrophic Lateral Sclerosis / genetics*
  • Ataxins
  • Case-Control Studies
  • Cohort Studies
  • Female
  • Genetic Linkage
  • Genetic Predisposition to Disease / epidemiology
  • Genetic Predisposition to Disease / ethnology
  • Genetic Predisposition to Disease / genetics*
  • Humans
  • Male
  • Middle Aged
  • Nerve Tissue Proteins / genetics*
  • Risk Factors
  • Spinocerebellar Ataxias / epidemiology
  • Spinocerebellar Ataxias / ethnology
  • Spinocerebellar Ataxias / genetics
  • Trinucleotide Repeat Expansion / genetics*
  • Young Adult

Substances

  • Ataxins
  • Nerve Tissue Proteins