title: ATXN8 -62 G/A promoter polymorphism and risk of Taiwanese Parkinson's disease.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Life Science, National Taiwan Normal University, Taipei, Taiwan.
authors.forename: I-C
authors.initials: IC
authors.lastname: Chen
authors.forename: Y-R
authors.initials: YR
authors.lastname: Wu
authors.forename: S-J
authors.initials: SJ
authors.lastname: Yang
authors.forename: S-H
authors.initials: SH
authors.lastname: Kao
authors.forename: Y-C
authors.initials: YC
authors.lastname: Chen
authors.forename: K-H
authors.initials: KH
authors.lastname: Chang
authors.forename: C-M
authors.initials: CM
authors.lastname: Lee
authors.forename: G-J
authors.initials: GJ
authors.lastname: Lee-Chen
authors.forename: C-M
authors.initials: CM
authors.lastname: Chen
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015153:Blotting, Western; D016022:Case-Control Studies; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D010300:Parkinson Disease / Q000235:genetics*; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic / Q000235:genetics*; D012307:Risk Factors; D013624:Taiwan; D055815:Young Adult
chemical_list: C539186:ATXN8 protein, human; D009419:Nerve Tissue Proteins