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Complex interactions in Parkinson's disease: A two-phased approach

✍ Scribed by Demetrius M. Maraganore; Mariza de Andrade; Timothy G. Lesnick; Matthew J. Farrer; James H. Bower; John A. Hardy; Walter A. Rocca

Publisher
John Wiley and Sons
Year
2003
Tongue
English
Weight
78 KB
Volume
18
Category
Article
ISSN
0885-3185

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✦ Synopsis

Abstract

The identification of pathogenic mutations in the three genes α‐synuclein, parkin, and ubiquitin carboxy‐terminal hydrolase L1 (UCHL1) has elucidated the ubiquitin proteasome system (UPS) and its potential role as a causal pathway in Parkinson's disease (PD). In addition, polymorphisms of these three genes have been shown to be independently associated with PD. In a sample of 298 unrelated PD cases and 185 controls, we applied a two‐phased approach of recursive partitioning and logistic regression analyses to explore complex interactions. For women only, we observed an epistatic interaction of UCHL1 and α‐synuclein genotypes with significant effects on PD risk (odds ratio = 2.42; P = 0.003). Our findings are consistent with the hypothesis that PD is a multigenic disorder of the UPS. © 2003 Movement Disorder Society

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