Association of Long ATXN2 CAG Repeat Sizes With Increased Risk of Amyotrophic Lateral Sclerosis

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)_nalleles of theATXN2gene (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 betweenATXN2high-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 supportATXN2high-length repeats as a risk factor for ALS and further indicate a genetic link between spinocerebellar ataxia type 2 and ALS.