Shujun Jiao1, Puzhi Wang1, Zhao Chen2, Chunrong Wang3, Yuting Shi1, Rong Qiu4, Beisha Tang5, Hong Jiang6. 1. Department of Neurology, Xiangya Hospital, Central South University, Changsha, China. 2. Department of Neurology, Xiangya Hospital, Central South University, Changsha, China; National Clinical Research Center for Geriatric Diseases, Central South University, Changsha, China; Key Laboratory of Hunan Province in Neurodegenerative Disorders, Central South University, Changsha, China. 3. Department of Pathology, Xiangya Hospital, Central South University, Changsha, China. 4. School of Information Science and Engineering, Central South University, Changsha, China. 5. Department of Neurology, Xiangya Hospital, Central South University, Changsha, China; National Clinical Research Center for Geriatric Diseases, Central South University, Changsha, China; Key Laboratory of Hunan Province in Neurodegenerative Disorders, Central South University, Changsha, China; Laboratory of Medical Genetics, Central South University, Changsha, China. 6. Department of Neurology, Xiangya Hospital, Central South University, Changsha, China; National Clinical Research Center for Geriatric Diseases, Central South University, Changsha, China; Key Laboratory of Hunan Province in Neurodegenerative Disorders, Central South University, Changsha, China; Laboratory of Medical Genetics, Central South University, Changsha, China. Electronic address: jianghong73868@126.com.
Abstract
OBJECTIVE: This study aimed to investigate factors modulating spinocerebellar ataxia type 3 (SCA3) phenotype severity besides the expanded CAG repeats (ExpCAG) of ATXN3. METHODS: Data regarding CAG trinucleotide repeats, age at onset (AO), duration, age, sex, transmitting parent, and scale scores of SCA3 patients were collected. Multiple linear regression analysis was performed to identify influential independent variables. Age, AO, ExpCAG, and duration were considered control variables to analyze the correlation between independent variables and scale scores. RESULTS: Duration, age, and ExpCAG were screened as influential independent variables (P = 0.000). Age had the greatest impact on multiple linear regression models (P<5E-8). ExpCAG and SARA/ICARS/INAS/Barthel index were not correlated (P > 0.05); considering only age as the control, ExpCAG was slightly-to-moderately correlated with all aforementioned scores except INAS (P < 0.05). Age and all scores, except INAS, were positively correlated (P < 0.05); considering duration, AO, or ExpCAG as controls, their correlations did not change significantly. On controlling age, AO was negatively correlated with all scores (P < 0.05), except for the Barthel index (P > 0.05). Furthermore, the interaction model revealed that the interaction between age, duration, and ExpCAG was significantly associated with SCA3 disease severity (P < 0.05). CONCLUSION: Age is a potentially important modifier of SCA3 phenotype severity, through the interaction between ExpCAG and aging factors.
OBJECTIVE: This study aimed to investigate factors modulating spinocerebellar ataxia type 3 (SCA3) phenotype severity besides the expanded CAG repeats (ExpCAG) of ATXN3. METHODS: Data regarding CAG trinucleotide repeats, age at onset (AO), duration, age, sex, transmitting parent, and scale scores of SCA3patients were collected. Multiple linear regression analysis was performed to identify influential independent variables. Age, AO, ExpCAG, and duration were considered control variables to analyze the correlation between independent variables and scale scores. RESULTS: Duration, age, and ExpCAG were screened as influential independent variables (P = 0.000). Age had the greatest impact on multiple linear regression models (P<5E-8). ExpCAG and SARA/ICARS/INAS/Barthel index were not correlated (P > 0.05); considering only age as the control, ExpCAG was slightly-to-moderately correlated with all aforementioned scores except INAS (P < 0.05). Age and all scores, except INAS, were positively correlated (P < 0.05); considering duration, AO, or ExpCAG as controls, their correlations did not change significantly. On controlling age, AO was negatively correlated with all scores (P < 0.05), except for the Barthel index (P > 0.05). Furthermore, the interaction model revealed that the interaction between age, duration, and ExpCAG was significantly associated with SCA3 disease severity (P < 0.05). CONCLUSION:Age is a potentially important modifier of SCA3 phenotype severity, through the interaction between ExpCAG and aging factors.