ATXN8 -62 G/A promoter polymorphism and risk of Taiwanese Parkinson's disease

I. C. Chen, Y. R. Wu, S. J. Yang, S. H. Kao, Y. C. Chen, K. H. Chang, C. M. Lee, G. J. Lee-Chen*, C. M. Chen


研究成果: 雜誌貢獻期刊論文同行評審

4 引文 斯高帕斯(Scopus)


Background and purpose: We recently reported a novel -62 G/A polymorphism within ataxin 8 (ATXN8) gene promoter region, with -62 G displaying significantly higher luciferase activity compared with -62 A. Phenotypic variability in spinocerebellar ataxia type 8 (SCA8) has been suggested, and large SCA8 repeats were found in patients with Parkinson's disease (PD). We aimed to investigate the association of ATXN8 -62 G/A polymorphism with the risk of Taiwanese PD, and identify the trans-acting factor modulating the ATXN8 promoter activity. Methods: A case-control study in a cohort of 569 PD cases and 547 ethnically matched controls was conducted by polymerase chain reaction (PCR) and restriction enzyme analysis. The trans-acting factor binding to the ATXN8 promoter was examined by chromatin immunoprecipitation (ChIP)-PCR assay, cDNA co-transfection and luciferase reporter assay. Results: When genotype distribution was calculated by comparing the rare AA genotype with the GG + GA genotypes (recessive model), a significant difference was found (P = 0.035, 1 df). Individuals carrying AA genotype exhibited a decreased risk of developing PD (odds ratio: 0.73; 95% CI: 0.55-0.98, P = 0.035). After stratification by age, individuals over 60 years of age carrying AA genotype demonstrated a further decrease in the risk of developing PD (odds ratio: 0.64; 95% CI: 0.43-0.96, P = 0.030). ChIP-PCR and cDNA over-expression revealed that CCAAT/enhancer-binding protein alpha binds to the ATXN8 proximal promoter to upregulate ATXN8 expression in neuroblastoma SK-N-SH cells. Conclusions: Our data suggest that ATXN8 -62 G/A polymorphism plays a role in Taiwanese PD susceptibility.

頁(從 - 到)1462-1469
期刊European Journal of Neurology
出版狀態已發佈 - 2012 11月

ASJC Scopus subject areas

  • 神經內科
  • 神經病學(臨床)


深入研究「ATXN8 -62 G/A promoter polymorphism and risk of Taiwanese Parkinson's disease」主題。共同形成了獨特的指紋。