P Wang1, Z Chen1, Y Peng1, L Cao2, X Li3, C Wang1, H Yang1, H Peng1, Y Shi1, X Zhou1, T Li1, L Feng3, C Wu3, R Qiu4, K Xia5, B Tang1,5,6,7,8,9,10, H Jiang1,5,6,7,11. 1. Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan, China. 2. Department of Neurology and Institute of Neurology, Rui Jin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China. 3. Department of Neurology, First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China. 4. School of Information Science and Engineering, Central South University, Changsha, Hunan, China. 5. Center for Medical Genetics, Central South University, Changsha, Hunan, China. 6. National Clinical Research Center for Geriatric Diseases, Central South University, Changsha, Hunan, China. 7. Key Laboratory of Hunan Province in Neurodegenerative Disorders, Central South University, Changsha, Hunan, China. 8. Parkinson's Disease Center of Beijing Institute for Brain Disorders, Beijing, China. 9. Collaborative Innovation Center for Brain Science, Shanghai, China. 10. Collaborative Innovation Center for Genetics and Development, Shanghai, China. 11. Xinjiang Medical University, Xinjiang, China.
Abstract
BACKGROUND AND PURPOSE: The expanded repeat length in ATXN1 negatively correlates with age at onset (AAO) of spinocerebellar ataxia type 1 (SCA1) but can explain only part of it, indicating that other factors affect AAO. Some studies have explored the influence of non-causative CAG repeats on the AAO of SCA patients. However, studies on Chinese SCA1 patients regarding candidate modifier factors involved in the variability in AAO are rare. METHODS: In all, 152 Chinese SCA1 patients who were genotyped for ATXN1 and nine other (CAG)n -containing genes were enrolled. Regression analysis was performed to determine the effect of the expanded allele of ATXN1 (linear and quadratic effects) on AAO. Then, different models were used to explore the modulatory effect of nine other (CAG)n -containing genes. RESULTS: Our results verified the negative effect of the expanded allele in ATXN1 by regression analysis. Some (CAG)n -containing genes including TBP, ATN1 and HTT modified AAO with variance ranging from 0.8% to 3.8% and tended to decrease or delay AAO. However, no modifier effects of ATXN2, ATXN3, CACNA1A, ATXN7, KCNN3, RAI1 and normal ATXN1 alleles in trans were detected. CONCLUSION: By using interaction analyses, TBP, ATN1 and HTT were determined to have modifying effects. Our study revealed that differences in modulation may be due to ethnic and geographic diversity across different populations. Furthermore, the variability of AAO was not completely explained by the genetic modifiers examined here, suggesting that other genetic or environmental factors are involved in these diseases.
BACKGROUND AND PURPOSE: The expanded repeat length in ATXN1 negatively correlates with age at onset (AAO) of spinocerebellar ataxia type 1 (SCA1) but can explain only part of it, indicating that other factors affect AAO. Some studies have explored the influence of non-causative CAG repeats on the AAO of SCApatients. However, studies on Chinese SCA1patients regarding candidate modifier factors involved in the variability in AAO are rare. METHODS: In all, 152 Chinese SCA1patients who were genotyped for ATXN1 and nine other (CAG)n -containing genes were enrolled. Regression analysis was performed to determine the effect of the expanded allele of ATXN1 (linear and quadratic effects) on AAO. Then, different models were used to explore the modulatory effect of nine other (CAG)n -containing genes. RESULTS: Our results verified the negative effect of the expanded allele in ATXN1 by regression analysis. Some (CAG)n -containing genes including TBP, ATN1 and HTT modified AAO with variance ranging from 0.8% to 3.8% and tended to decrease or delay AAO. However, no modifier effects of ATXN2, ATXN3, CACNA1A, ATXN7, KCNN3, RAI1 and normal ATXN1 alleles in trans were detected. CONCLUSION: By using interaction analyses, TBP, ATN1 and HTT were determined to have modifying effects. Our study revealed that differences in modulation may be due to ethnic and geographic diversity across different populations. Furthermore, the variability of AAO was not completely explained by the genetic modifiers examined here, suggesting that other genetic or environmental factors are involved in these diseases.