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

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 >or=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 >or=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 >or=60 years of age, or acting synergistically with USP40 and UCHL1 in the total subjects.

• Authors: 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-Chen
• Journal: Clinica chimica acta; international journal of clinical chemistry (Clin Chim Acta) Vol. 411 Issue 13-14 Pg. 955-8 (Jul 04 2010) ISSN: 1873-3492 [Electronic] Netherlands
• PMID: 20302855 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright 2010 Elsevier B.V. All rights reserved.

Chemical References

• UCHL1 protein, human
• USP24 protein, human
• USP40 protein, human
• Ubiquitin Thiolesterase

Topics

• Adult
• Aged
• Aged, 80 and over
• Alleles
• Asian People (genetics)
• Case-Control Studies
• Female
• Genetic Predisposition to Disease
• Genotype
• Humans
• Male
• Middle Aged
• Multivariate Analysis
• Parkinson Disease (genetics)
• Polymorphism, Genetic
• Taiwan
• Ubiquitin Thiolesterase (genetics)
• Young Adult