Intermediate-length polyglutamine in ATXN2 is a possible risk factor among Eastern Chinese patients with amyotrophic lateral sclerosis

Hai-Peng Lu; Shi-Rui Gan; Sheng Chen; Hong-Fu Li; Zhi-Jun Liu; Wang Ni; Ning Wang; Zhi-Ying Wu

doi:10.1016/j.neurobiolaging.2014.10.015

Intermediate-length polyglutamine in ATXN2 is a possible risk factor among Eastern Chinese patients with amyotrophic lateral sclerosis

Neurobiol Aging. 2015 Mar;36(3):1603.e11-4. doi: 10.1016/j.neurobiolaging.2014.10.015. Epub 2014 Oct 16.

Authors

Hai-Peng Lu¹, Shi-Rui Gan², Sheng Chen², Hong-Fu Li³, Zhi-Jun Liu⁴, Wang Ni⁵, Ning Wang², Zhi-Ying Wu⁶

Affiliations

¹ Department of Neurology and Institute of Neurology, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China; Department of Neurology and Institute of Neurology, First Affiliated Hospital, Fujian Medical University, Fuzhou, China; Department of Neurology, Jinhua Hospital, Zhejiang University, Jinhua, China.
² Department of Neurology and Institute of Neurology, First Affiliated Hospital, Fujian Medical University, Fuzhou, China.
³ Department of Neurology and Institute of Neurology, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
⁴ Department of Neurology and Institute of Neurology, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China.
⁵ Department of Neurology and Institute of Neurology, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China; Department of Neurology and Institute of Neurology, First Affiliated Hospital, Fujian Medical University, Fuzhou, China; Department of Neurology and Institute of Neurology, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China.
⁶ Department of Neurology and Institute of Neurology, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China; Department of Neurology and Institute of Neurology, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China. Electronic address: zhiyingwu67@yahoo.com.

PMID: 25457026
DOI: 10.1016/j.neurobiolaging.2014.10.015

Abstract

An effective treatment for amyotrophic lateral sclerosis (ALS) has not yet been found because the pathogenesis of this fatal disease is not well understood. A number of previous studies demonstrated that intermediate-length polyglutamine repeats within the ataxin-2 gene (ATXN2) might be a risk factor among patients with ALS in Western countries. Here, we aim to determine whether this sequence is a risk factor in Eastern Chinese ALS patients. Therefore, 379 unrelated sporadic ALS patients, 15 unrelated familial ALS patients, and 900 neurologically normal controls were studied. The ATXN2 CAG repeats were amplified using polymerase chain reaction. The products were separated on an 8% polyacrylamide gel and confirmed using Sanger sequencing. The results were evaluated using SPSS 17.0. We found that ATXN2 intermediate-length polyglutamine expansions greater than 24 and 27 repeats were associated with sporadic ALS. Our finding supports the hypothesis that ATXN2 plays an important role in the pathogenesis of ALS.

Keywords: ATXN2; Amyotrophic lateral sclerosis; Association; Chinese.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adolescent
Adult
Aged
Amyotrophic Lateral Sclerosis / genetics*
Asian People / genetics
Ataxin-2 / chemistry
Ataxin-2 / genetics*
Female
Genetic Association Studies*
Genetic Predisposition to Disease / genetics*
Humans
Male
Middle Aged
Peptides / genetics*
Risk Factors
Trinucleotide Repeat Expansion*
Young Adult

Substances

ATXN2 protein, human
Ataxin-2
Peptides
polyglutamine