Ubiquitin specific proteases USP24 and USP40 and ubiquitin thiolesterase UCHL1 polymorphisms have synergic effect on the risk of Parkinson's disease among Taiwanese

Yih Ru Wu, Chiung Mei Chen, Yi Chun Chen, Chih Ying Chao, Long Sun Ro, Hon Chung Fung, Ya Chin Hsiao, Fen Ju Hu, Guey-Jen Lee

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

Background: Impaired ubiquitin-proteasome system function may contribute to the pathogenesis of Parkinson's disease (PD). Methods: We conducted a case-control study in a cohort of 517 PD cases and 518 ethnically matched controls to investigate the association of ubiquitin specific proteases USP24 rs487230 C>T, USP40 rs1048603 C>T, and ubiquitin thiolesterase UCHL1 rs5030732 A>C polymorphisms with the risk of PD. Results: No significant difference in the genotype or allele distribution was found between PD and controls. After stratification by age, the genotype and allele frequencies of USP24 rs487230 are significantly different between PD and controls >60. years of age (P=0.035 and 0.013, respectively). Multivariable logistic regression with adjusting for onset age and sex showed that, in a dominant model, USP24 T-carrying genotype was associated with risk reduction in developing PD in individuals >60. years of age (OR=0.61; 95% CI=0.41-0.90, P=0.010). This is also true for T allele (OR=0.64; 95% CI=0.44-0.91, P=0.023). When examining the interaction between genes on PD risk without age stratification, the protective effect of USP24 CT/TT genotype on PD risks was strengthened by the USP40 T-carrying genotype (OR=0.42; 95% CI=0.22-0.81, P=0.009) and UCHL1 C-carrying genotype (OR=0.67; 95% CI=0.47-0.97, P=0.032). Conclusions: Our results suggest that USP24 alone plays a role in PD susceptibility among Taiwanese people >60. years of age, or acting synergistically with USP40 and UCHL1 in the total subjects.

Original languageEnglish
Pages (from-to)955-958
Number of pages4
JournalClinica Chimica Acta
Volume411
Issue number13-14
DOIs
Publication statusPublished - 2010 Jul 1

Fingerprint

Ubiquitin Thiolesterase
Ubiquitin-Specific Proteases
Polymorphism
Parkinson Disease
Genotype
Alleles
Disease Susceptibility
Proteasome Endopeptidase Complex
Risk Reduction Behavior
Ubiquitin
Age of Onset
Gene Frequency
Logistics
Case-Control Studies
Genes
Logistic Models

Keywords

  • Disease association
  • Parkinson's disease
  • SNP
  • UCHL1
  • USP24
  • USP40

ASJC Scopus subject areas

  • Biochemistry
  • Clinical Biochemistry
  • Biochemistry, medical

Cite this

Ubiquitin specific proteases USP24 and USP40 and ubiquitin thiolesterase UCHL1 polymorphisms have synergic effect on the risk of Parkinson's disease among Taiwanese. / Wu, Yih Ru; Chen, Chiung Mei; Chen, Yi Chun; Chao, Chih Ying; Ro, Long Sun; Fung, Hon Chung; Hsiao, Ya Chin; Hu, Fen Ju; Lee, Guey-Jen.

In: Clinica Chimica Acta, Vol. 411, No. 13-14, 01.07.2010, p. 955-958.

Research output: Contribution to journalArticle

Wu, Yih Ru ; Chen, Chiung Mei ; Chen, Yi Chun ; Chao, Chih Ying ; Ro, Long Sun ; Fung, Hon Chung ; Hsiao, Ya Chin ; Hu, Fen Ju ; Lee, Guey-Jen. / Ubiquitin specific proteases USP24 and USP40 and ubiquitin thiolesterase UCHL1 polymorphisms have synergic effect on the risk of Parkinson's disease among Taiwanese. In: Clinica Chimica Acta. 2010 ; Vol. 411, No. 13-14. pp. 955-958.
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T1 - Ubiquitin specific proteases USP24 and USP40 and ubiquitin thiolesterase UCHL1 polymorphisms have synergic effect on the risk of Parkinson's disease among Taiwanese

AU - Wu, Yih Ru

AU - Chen, Chiung Mei

AU - Chen, Yi Chun

AU - Chao, Chih Ying

AU - Ro, Long Sun

AU - Fung, Hon Chung

AU - Hsiao, Ya Chin

AU - Hu, Fen Ju

AU - Lee, Guey-Jen

PY - 2010/7/1

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N2 - Background: Impaired ubiquitin-proteasome system function may contribute to the pathogenesis of Parkinson's disease (PD). Methods: We conducted a case-control study in a cohort of 517 PD cases and 518 ethnically matched controls to investigate the association of ubiquitin specific proteases USP24 rs487230 C>T, USP40 rs1048603 C>T, and ubiquitin thiolesterase UCHL1 rs5030732 A>C polymorphisms with the risk of PD. Results: No significant difference in the genotype or allele distribution was found between PD and controls. After stratification by age, the genotype and allele frequencies of USP24 rs487230 are significantly different between PD and controls >60. years of age (P=0.035 and 0.013, respectively). Multivariable logistic regression with adjusting for onset age and sex showed that, in a dominant model, USP24 T-carrying genotype was associated with risk reduction in developing PD in individuals >60. years of age (OR=0.61; 95% CI=0.41-0.90, P=0.010). This is also true for T allele (OR=0.64; 95% CI=0.44-0.91, P=0.023). When examining the interaction between genes on PD risk without age stratification, the protective effect of USP24 CT/TT genotype on PD risks was strengthened by the USP40 T-carrying genotype (OR=0.42; 95% CI=0.22-0.81, P=0.009) and UCHL1 C-carrying genotype (OR=0.67; 95% CI=0.47-0.97, P=0.032). Conclusions: Our results suggest that USP24 alone plays a role in PD susceptibility among Taiwanese people >60. years of age, or acting synergistically with USP40 and UCHL1 in the total subjects.

AB - Background: Impaired ubiquitin-proteasome system function may contribute to the pathogenesis of Parkinson's disease (PD). Methods: We conducted a case-control study in a cohort of 517 PD cases and 518 ethnically matched controls to investigate the association of ubiquitin specific proteases USP24 rs487230 C>T, USP40 rs1048603 C>T, and ubiquitin thiolesterase UCHL1 rs5030732 A>C polymorphisms with the risk of PD. Results: No significant difference in the genotype or allele distribution was found between PD and controls. After stratification by age, the genotype and allele frequencies of USP24 rs487230 are significantly different between PD and controls >60. years of age (P=0.035 and 0.013, respectively). Multivariable logistic regression with adjusting for onset age and sex showed that, in a dominant model, USP24 T-carrying genotype was associated with risk reduction in developing PD in individuals >60. years of age (OR=0.61; 95% CI=0.41-0.90, P=0.010). This is also true for T allele (OR=0.64; 95% CI=0.44-0.91, P=0.023). When examining the interaction between genes on PD risk without age stratification, the protective effect of USP24 CT/TT genotype on PD risks was strengthened by the USP40 T-carrying genotype (OR=0.42; 95% CI=0.22-0.81, P=0.009) and UCHL1 C-carrying genotype (OR=0.67; 95% CI=0.47-0.97, P=0.032). Conclusions: Our results suggest that USP24 alone plays a role in PD susceptibility among Taiwanese people >60. years of age, or acting synergistically with USP40 and UCHL1 in the total subjects.

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