Two novel SNPs in ATXN3 3' UTR may decrease age at onset of SCA3/MJD in Chinese patients

Zhe Long; Zhao Chen; Chunrong Wang; Fengzhen Huang; Huirong Peng; Xuan Hou; Dongxue Ding; Wei Ye; Junling Wang; Qian Pan; Jiada Li; Kun Xia; Beisha Tang; Tetsuo Ashizawa; Hong Jiang

doi:10.1371/journal.pone.0117488

Two novel SNPs in ATXN3 3' UTR may decrease age at onset of SCA3/MJD in Chinese patients

PLoS One. 2015 Feb 17;10(2):e0117488. doi: 10.1371/journal.pone.0117488. eCollection 2015.

Authors

Zhe Long¹, Zhao Chen¹, Chunrong Wang², Fengzhen Huang³, Huirong Peng¹, Xuan Hou¹, Dongxue Ding¹, Wei Ye¹, Junling Wang⁴, Qian Pan⁵, Jiada Li⁵, Kun Xia⁵, Beisha Tang⁴, Tetsuo Ashizawa⁶, Hong Jiang⁴

Affiliations

¹ Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, P. R. China.
² Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, P. R. China; Department of Neurology, Xiangtan Central Hospital, Xiangtan, Hunan 411100, P. R. China.
³ Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, P. R. China; Department of Neurology & Institute of Translational Medicine at University of South China, the First People's Hospital of Chenzhou, Chenzhou, Hunan 423000, P. R. China.
⁴ Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, P. R. China; Key Laboratory of Hunan Province in Neurodegenerative Disorders, Central South University, Changsha, Hunan 410008, P. R. China; State Key Lab of Medical Genetics, Central South University, Changsha, Hunan 410078, P. R. China.
⁵ State Key Lab of Medical Genetics, Central South University, Changsha, Hunan 410078, P. R. China.
⁶ Department of Neurology, University of Florida, Gainesville, Florida, United States of America.

Abstract

Spinocerebellar ataxia type 3 (SCA3), or Machado-Joseph disease (MJD), is an autosomal dominantly-inherited disease that produces progressive problems with movement. It is caused by the expansion of an area of CAG repeats in a coding region of ATXN3. The number of repeats is inversely associated with age at disease onset (AO) and is significantly associated with disease severity; however, the degree of CAG expansion only explains 50 to 70% of variance in AO. We tested two SNPs, rs709930 and rs910369, in the 3' UTR of ATXN3 gene for association with SCA3/MJD risk and with SCA3/MJD AO in an independent cohort of 170 patients with SCA3/MJD and 200 healthy controls from mainland China. rs709930 genotype frequencies were statistically significantly different between patients and controls (p = 0.001, α = 0.05). SCA3/MJD patients carrying the rs709930 A allele and rs910369 T allele experienced an earlier onset, with a decrease in AO of approximately 2 to 4 years. The two novel SNPs found in this study might be genetic modifiers for AO in SCA3/MJD.

Publication types

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

MeSH terms

3' Untranslated Regions*
Adolescent
Adult
Age of Onset
Aged
Alleles
Asian People / genetics
Ataxin-3 / genetics*
China
Female
Gene Frequency
Genotype
Humans
Machado-Joseph Disease / genetics*
Male
Middle Aged
Mutation
Polymorphism, Single Nucleotide*
Young Adult

Substances

3' Untranslated Regions
Ataxin-3

Grants and funding

This study was supported by the National Basic Research Program (973 Program) (Nos. 2012CB944601, 2012CB517902 and 2011CB510002 to Hong Jiang), the New Century Excellent Talents in University (No. NCET-10-0836 to Hong Jiang), the National Natural Science Foundation of China (Nos. 81410308019, 81471156, 81271260, 30971585 to Hong Jiang), Hunan Funds for Distinguished Young Scientists (No. 14JJ1008 to Hong Jiang), Xinjiang Natural Science Foundation (No. 201318101-4 to Hong Jiang), the Undergraduate Innovation Project of Central South University (No. YB13028, 201410533324 to Hong Jiang), Graduate Innovation Project of Central South University (No. 2014zzts078 to Zhao Chen) and High-Level Medical Personnel of Hunan Province 225 Project. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.