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

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)1462-1469
Number of pages8
JournalEuropean Journal of Neurology
Volume19
Issue number11
DOIs
Publication statusPublished - 2012 Nov 1

Fingerprint

Parkinson Disease
Genotype
Trans-Activators
Chromatin Immunoprecipitation
Luciferases
Polymerase Chain Reaction
Complementary DNA
Odds Ratio
CCAAT-Enhancer-Binding Protein-alpha
Restriction Mapping
Disease Susceptibility
Neuroblastoma
Genetic Promoter Regions
Transfection
Case-Control Studies
Up-Regulation
Genes
Spinocerebellar ataxia 8

Keywords

  • -62 G/A polymorphism
  • ATXN8
  • CCAAT/enhancer-binding protein alpha
  • Case-control study
  • Parkinson's disease

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

Cite this

Chen, I. C., Wu, Y. R., Yang, S. J., Kao, S. H., Chen, Y. C., Chang, K. H., ... Chen, C. M. (2012). ATXN8 -62 G/A promoter polymorphism and risk of Taiwanese Parkinson's disease. European Journal of Neurology, 19(11), 1462-1469. https://doi.org/10.1111/j.1468-1331.2012.03749.x

ATXN8 -62 G/A promoter polymorphism and risk of Taiwanese Parkinson's disease. / Chen, I. C.; Wu, Y. R.; Yang, S. J.; Kao, S. H.; Chen, Y. C.; Chang, K. H.; Lee, C. M.; Lee-Chen, G. J.; Chen, C. M.

In: European Journal of Neurology, Vol. 19, No. 11, 01.11.2012, p. 1462-1469.

Research output: Contribution to journalArticle

Chen, IC, Wu, YR, Yang, SJ, Kao, SH, Chen, YC, Chang, KH, Lee, CM, Lee-Chen, GJ & Chen, CM 2012, 'ATXN8 -62 G/A promoter polymorphism and risk of Taiwanese Parkinson's disease', European Journal of Neurology, vol. 19, no. 11, pp. 1462-1469. https://doi.org/10.1111/j.1468-1331.2012.03749.x
Chen, I. C. ; Wu, Y. R. ; Yang, S. J. ; Kao, S. H. ; Chen, Y. C. ; Chang, K. H. ; Lee, C. M. ; Lee-Chen, G. J. ; Chen, C. M. / ATXN8 -62 G/A promoter polymorphism and risk of Taiwanese Parkinson's disease. In: European Journal of Neurology. 2012 ; Vol. 19, No. 11. pp. 1462-1469.
@article{2a5274bfee8540c1b195e70fc7d5603b,
title = "ATXN8 -62 G/A promoter polymorphism and risk of Taiwanese Parkinson's disease",
abstract = "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.",
keywords = "-62 G/A polymorphism, ATXN8, CCAAT/enhancer-binding protein alpha, Case-control study, Parkinson's disease",
author = "Chen, {I. C.} and Wu, {Y. R.} and Yang, {S. J.} and Kao, {S. H.} and Chen, {Y. C.} and Chang, {K. H.} and Lee, {C. M.} and Lee-Chen, {G. J.} and Chen, {C. M.}",
year = "2012",
month = "11",
day = "1",
doi = "10.1111/j.1468-1331.2012.03749.x",
language = "English",
volume = "19",
pages = "1462--1469",
journal = "European Journal of Neurology",
issn = "1351-5101",
publisher = "Wiley-Blackwell",
number = "11",

}

TY - JOUR

T1 - ATXN8 -62 G/A promoter polymorphism and risk of Taiwanese Parkinson's disease

AU - Chen, I. C.

AU - Wu, Y. R.

AU - Yang, S. J.

AU - Kao, S. H.

AU - Chen, Y. C.

AU - Chang, K. H.

AU - Lee, C. M.

AU - Lee-Chen, G. J.

AU - Chen, C. M.

PY - 2012/11/1

Y1 - 2012/11/1

N2 - 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.

AB - 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.

KW - -62 G/A polymorphism

KW - ATXN8

KW - CCAAT/enhancer-binding protein alpha

KW - Case-control study

KW - Parkinson's disease

UR - http://www.scopus.com/inward/record.url?scp=84867686204&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84867686204&partnerID=8YFLogxK

U2 - 10.1111/j.1468-1331.2012.03749.x

DO - 10.1111/j.1468-1331.2012.03749.x

M3 - Article

C2 - 22577844

AN - SCOPUS:84867686204

VL - 19

SP - 1462

EP - 1469

JO - European Journal of Neurology

JF - European Journal of Neurology

SN - 1351-5101

IS - 11

ER -