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ATXN 8 −62 G/A promoter polymorphism and risk of T aiwanese P arkinson's disease
Author(s) -
Chen I.C.,
Wu Y.R.,
Yang S.J.,
Kao S.H.,
Chen Y.C.,
Chang K.H.,
Lee C.M.,
LeeChen G.J.,
Chen C.M.
Publication year - 2012
Publication title -
european journal of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.881
H-Index - 124
eISSN - 1468-1331
pISSN - 1351-5101
DOI - 10.1111/j.1468-1331.2012.03749.x
Subject(s) - genotype , promoter , odds ratio , microbiology and biotechnology , chromatin immunoprecipitation , medicine , spinocerebellar ataxia , biology , genetics , gene , gene expression
Background and purpose We recently reported a novel −62 G/A polymorphism within ataxin 8 ( ATXN 8) gene promoter region, with −62 G displaying significantly higher luciferase activity compared with −62 A . Phenotypic variability in spinocerebellar ataxia type 8 ( SCA 8) has been suggested, and large SCA 8 repeats were found in patients with P arkinson's disease ( PD ). We aimed to investigate the association of ATXN 8 −62 G/A polymorphism with the risk of T aiwanese PD , and identify the trans ‐acting factor modulating the ATXN 8 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 ATXN 8 promoter was examined by chromatin immunoprecipitation ( C h IP )‐ PCR assay, c DNA 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). C h IP ‐ PCR and c DNA over‐expression revealed that CCAAT /enhancer‐binding protein alpha binds to the ATXN 8 proximal promoter to upregulate ATXN 8 expression in neuroblastoma SK ‐ N ‐ SH cells. Conclusions Our data suggest that ATXN 8 −62 G/A polymorphism plays a role in T aiwanese PD susceptibility.