Sheng Chen1,2, Shi-Rui Gan3, Ping-Ping Cai3, Wang Ni1, Qi Zhou3, Yi Dong2, Ning Wang3, Zhi-Ying Wu1. 1. 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. 2. Department of Neurology and Institute of Neurology, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China. 3. Department of Neurology and Institute of Neurology, First Affiliated Hospital, Fujian Medical University, Fuzhou, China.
Abstract
AIMS: 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. CONCLUSION: 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.
AIMS: 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 MJDpatients 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. CONCLUSION: Six candidate SNPs have been screened in Chinese patients with MJD. A remarkable earlier AAO was noted in male Chinese MJDpatients with MT-ND3 gene 10398A polymorphism.
Authors: Nester Mitchell; Gaynel A LaTouche; Beverly Nelson; Karla P Figueroa; Ruth H Walker; Andrew K Sobering Journal: Tremor Other Hyperkinet Mov (N Y) Date: 2019-09-13