Mitochondrial NADH Dehydrogenase Subunit 3 Polymorphism Associated with an Earlier Age at Onset in Male Machado-Joseph disease Patients.
OBJECTIVE
To investigate the potential effect of six previously reported candidate single nucleotide polymorphisms on age at onset (AAO) among Chinese patients with Machado-Joseph disease (MJD).


METHODS
Three hundred and twenty-four unrelated molecular-confirmed MJD patients were recruited between January 2006 and December 2014. The screening of candidate polymorphisms was first performed in 173 subjects using the SNaPshot(®) Multiplex System. The mitochondrial NADH dehydrogenase subunit 3 (MT-ND3) polymorphism 10398A>G (rs2853826) was further verified with Sanger sequencing in additional 151 patients.


RESULTS
An inverse correlation was found between expanded CAG repeat length and AAO. The expanded CAG repeat length can explain 63% of AAO variance. The 10398A polymorphism was significantly associated with a 3-year earlier AAO in male patients with MJD (P = 0.001). Stepwise multiple regressions revealed that the 10398A polymorphism could account for nearly 2% of AAO variance in male patients.


CONCLUSIONS
Six candidate SNPs have been screened in Chinese patients with MJD. A remarkable earlier AAO was noted in male Chinese MJD patients with MT-ND3 gene 10398A polymorphism.
Department of Neurology and Research Center of Neurology in Second Affiliated Hospital and the Collaborative Innovation Center for Brain Science, Zhejiang University School of Medicine, Hangzhou, China.|Department of Neurology and Institute of Neurology, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China.
Sheng
S
Chen
Department of Neurology and Institute of Neurology, First Affiliated Hospital, Fujian Medical University, Fuzhou, China.
Shi-Rui
SR
Gan
Department of Neurology and Institute of Neurology, First Affiliated Hospital, Fujian Medical University, Fuzhou, China.
Ping-Ping
PP
Cai
Department of Neurology and Research Center of Neurology in Second Affiliated Hospital and the Collaborative Innovation Center for Brain Science, Zhejiang University School of Medicine, Hangzhou, China.
Wang
W
Ni
Department of Neurology and Institute of Neurology, First Affiliated Hospital, Fujian Medical University, Fuzhou, China.
Qi
Q
Zhou
Department of Neurology and Institute of Neurology, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China.
Yi
Y
Dong
Department of Neurology and Institute of Neurology, First Affiliated Hospital, Fujian Medical University, Fuzhou, China.
Ning
N
Wang
Department of Neurology and Research Center of Neurology in Second Affiliated Hospital and the Collaborative Innovation Center for Brain Science, Zhejiang University School of Medicine, Hangzhou, China.
Zhi-Ying
ZY
Wu
D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D044466:Asian People / Q000235:genetics; D002681:China; D004252:DNA Mutational Analysis; D042967:Electron Transport Complex I / Q000235:genetics*; D005260:Female; D006801:Humans; D017827:Machado-Joseph Disease / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D019680:Trinucleotide Repeat Expansion; D055815:Young Adult
D042967:Electron Transport Complex I; C114961:MT-ND3 protein, human
ATXN3; Age at onset; CAG repeat; MJD; MT-ND3