Shi-Rui Gan1, Karla P Figueroa2, Hao-Ling Xu1, Susan Perlman3, George Wilmot4, Christopher M Gomez5, Jeremy Schmahmann6, Henry Paulson7, Vikram G Shakkottai7, Sarah H Ying8, Theresa Zesiewicz9, Khalaf Bushara10, Michael D Geschwind11, Guangbin Xia12, S H Subramony13, Liana Rosenthal14, Tetsuo Ashizawa15, Stefan M Pulst2, Ning Wang16, Sheng-Han Kuo17. 1. Department of Neurology and Institute of Neurology, First Affiliated Hospital, Fujian Medical University, Fuzhou, China. 2. Department of Neurology, University of Utah, Salt Lake City, UT, USA. 3. Department of Neurology, University of California, Los Angeles, CA, USA. 4. Department of Neurology, Emory University, Atlanta, GA, USA. 5. Department of Neurology, University of Chicago, Chicago, IL, USA. 6. Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA. 7. Department of Neurology, University of Michigan, Ann Arbor, MI, USA. 8. Department of Neurology, Johns Hopkins University, Baltimore, MD, USA. 9. Department of Neurology, University of South Florida, Tampa, FL, USA. 10. Department of Neurology, University of Minnesota, Minneapolis, MN, USA. 11. Department of Neurology, University of California, San Francisco, CA, USA. 12. Department of Neurology, School of Medicine, University of New Mexico, Albuquerque, NM, USA. 13. Department of Neurology and McKnight Brain Institute, University of Florida, Gainesville, FL, USA. 14. Department of Neurology, Johns Hopkins School of Medicine, Baltimore, MD, USA. 15. Houston Methodist Research Institute, Houston, TX, USA. 16. Department of Neurology and Institute of Neurology, First Affiliated Hospital, Fujian Medical University, Fuzhou, China. Electronic address: ningwang@mail.fjmu.edu.cn. 17. Department of Neurology, College of Physicians and Surgeons, Columbia University, New York, NY, USA. Electronic address: sk3295@columbia.edu.
Abstract
BACKGROUND: For a variety of sporadic neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease and amyotrophic lateral sclerosis, it is well-established that ethnicity does affect the disease phenotypes. However, how ethnicity contributes to the clinical symptoms and disease progressions in monogenetic disorders, such as spinocerebellar ataxia type 3 (SCA3), remains less studied. METHODS: We used multivariable linear and logistical regression models in 257 molecularly-confirmed SCA3 patients (66 Caucasians, 43 African Americans, and 148 Asians [composed of 131 Chinese and 17 Asian Americans]) to explore the influence of ethnicity on age at onset (AAO), ataxia severity, and non-ataxia symptoms (i.e. depression, tremor, and dystonia). RESULTS: We found that Asians had significantly later AAO, compared to Caucasians (β = 4.75, p = 0.000) and to African Americans (β = 6.64, p = 0.000) after adjusting for the pathological CAG repeat numbers in ATXN3. African Americans exhibited the most severe ataxia as compared to Caucasians (β = 3.81, p = 0.004) and Asians (β = 4.39, p = 0.001) after taking into consideration of the pathological CAG repeat numbers in ATXN3 and disease duration. Caucasians had a higher prevalence of depression than African Americans (β = 1.23, p = 0.040). Ethnicity had no influence on tremor or dystonia. CONCLUSIONS: Ethnicity plays an important role in clinical presentations of SCA3 patients, which could merit further clinical studies and public health consideration. These results highlight the role of ethnicity in monogenetic, neurodegenerative disorders.
BACKGROUND: For a variety of sporadic neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease and amyotrophic lateral sclerosis, it is well-established that ethnicity does affect the disease phenotypes. However, how ethnicity contributes to the clinical symptoms and disease progressions in monogenetic disorders, such as spinocerebellar ataxia type 3 (SCA3), remains less studied. METHODS: We used multivariable linear and logistical regression models in 257 molecularly-confirmed SCA3patients (66 Caucasians, 43 African Americans, and 148 Asians [composed of 131 Chinese and 17 Asian Americans]) to explore the influence of ethnicity on age at onset (AAO), ataxia severity, and non-ataxia symptoms (i.e. depression, tremor, and dystonia). RESULTS: We found that Asians had significantly later AAO, compared to Caucasians (β = 4.75, p = 0.000) and to African Americans (β = 6.64, p = 0.000) after adjusting for the pathological CAG repeat numbers in ATXN3. African Americans exhibited the most severe ataxia as compared to Caucasians (β = 3.81, p = 0.004) and Asians (β = 4.39, p = 0.001) after taking into consideration of the pathological CAG repeat numbers in ATXN3 and disease duration. Caucasians had a higher prevalence of depression than African Americans (β = 1.23, p = 0.040). Ethnicity had no influence on tremor or dystonia. CONCLUSIONS: Ethnicity plays an important role in clinical presentations of SCA3patients, which could merit further clinical studies and public health consideration. These results highlight the role of ethnicity in monogenetic, neurodegenerative disorders.
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