<b><i>UCH-L1</i></b> S18Y Variant and Risk of Parkinson's Disease in Asian Populations: An Updated Meta-Analysis

Abstract

The ubiquitin carboxy-terminal hydrolase L1 (UCH-L1) gene has been implicated in the etiology of Parkinson's disease (PD). Several studies have evaluated the association between the UCH-L1 S18Y variant and the risk of PD. However, conflicting results have been reported. Therefore, we performed a meta-analysis to explore whether the UCH-L1 S18Y variant is associated with susceptibility to PD in Asians. A database search in Web of Science, MEDLINE, Embase and PubMed up to March 2014 identified 10 studies comprising 4,897 PD patients and 4,446 controls in total, which were included in this meta-analysis. In an updated meta-analysis, no significant associations between the S18Y polymorphism and PD in Asians were observed in recessive [p = 0.28, odds ratio (OR) = 1.47, 95% confidence interval (CI): 0.86-1.04] or dominant models (p = 0.46, OR = 0.96, 95% CI: 0.88-1.06). In the subgroup analysis by ethnicity, still no significant association was detected in dominant (for Chinese, OR = 0.97, 95% CI: 0.85-1.10; for Japanese, OR = 0.96, 95% CI: 0.83-1.11) and recessive models (for Chinese, OR = 0.99, 95% CI: 0.88-1.11; for Japanese, OR = 0.89, 95% CI: 0.76-1.04). The results of this meta-analysis suggested that the UCHL-1 S18Y polymorphism was not associated with the risk of PD in Asians. To our knowledge, this is the latest and largest meta-analysis assessing the association of the UCHL-1 S18Y variant with the risk of PD in Asian ancestry.

Ubiquitin C-terminal Hydrolase L1 Regulates Lipid Raft-dependent Endocytosis

“…Down-regulation and extensive oxidative modification of UCH-L1 have been observed in the brains of AD and PD patients [ 3 ]. A missense mutation, I93M, in UCH-L1 has been identified in patients with autosomal dominant familial PD [ 4 ], and an S18Y mutation in UCH-L1 has been reported to exert a neuroprotective effect against PD [ 5 ], although these genetic studies are controversial [ 6 7 ].…”

Estudo dos efeitos da superexpressão da alfa-sinucleína sobre o tráfego mitocondrial e autofagia em leveduras, células SH-SY5Y e neurônios dopaminérgicos derivados de hiPSC de pacientes com doença de Parkinson

“…Autosomal dominant mutations in the alpha-synuclein gene (SNCA) can lead to duplication or triplication of the gene, generating several copies of alpha-synuclein. A30P (G88C) and A53T are examples of PD linked point mutations in the α-synuclein gene involving the replacement of alanine by proline or threonine, respectively, at the indicated sites (Vilageliu and Grinberg, 2016;Sudhaman et al, 2016;Park et al, 2015;Palmier et al, 2013;Ono et al, 2011;Lee et al, 2010;Narhi et al, 1999;Zhu et al, 2014).…”