Abstract
Although many case–control studies have investigated the association between a single UCHL1 S18Y gene polymorphism and the risk of Parkinson’s disease (PD), the results have been ambiguous. To evaluate the overall effect between published case–control studies of Asian subjects, we conducted a meta-analysis based on 11 studies including 3,971 PD cases and 3,721 controls. Studies carried out up to 30 April 2014, were identified using the databases PubMed, MEDLINE, EMBASE and Web of Knowledge. The crude odds ratios (ORs) with 95 % confidence intervals (95 % CI) were calculated to evaluate the association. The results of our meta-analysis indicated that the UCHL1 S18Y gene polymorphism does not correlate with the risk of PD (allele model: OR 0.93, 95 % CI 0.84–1.02; dominant model: OR 0.94, 95 % CI 0.86–1.04; recessive model: OR 0.90, 95 % CI 0.77–1.06; homozygous model: OR 0.86, 95 % CI 0.71–1.04). A similar result was observed in subgroup analysis of ethnicity, age at onset, genotype methods, Hardy–Weinberg equilibrium, and source of controls. Thus, the current meta-analysis suggests no evidence for the association between the UCHL1 S18Y polymorphism and PD risk in the Asian population, especially in subgroups of ethnicity and age at onset. Further studies with larger population sizes are needed to confirm this result.
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References
Forno LS (1996) Neuropathology of Parkinson’s disease. J Neuropathol Exp Neurol 55:259–272
de Rijk MC, Launer LJ, Berger K, Breteler MM et al (2000) Prevalence of Parkinson’s disease in Europe: a collaborative study of population-based cohorts. Neurology 54:S21–S23
Warner TT, Schapira AH (2003) Genetic and environmental factors in the cause of Parkinson’s disease. Ann Neurol 53:S16–S23
Ciechanover A, Brundin P (2003) The ubiquitin proteasome system in neurodegenerative diseases: sometimes the chicken, sometimes the egg. Neuron 40:427–446
Lim KL, Tan JM (2007) Role of the ubiquitin proteasome system in Parkinson’s disease. BMC Biochem 8:S13
Liu Y, Fallon L, Lashuel HA (2002) The UCH-L1 gene encodes two opposing enzymatic activities that affect alphasynuclein degradation and Parkinson’s disease susceptibility. Cell 111:209–218
Maraganore DM, Farrer MJ, Hardy JA (1999) Case–control study of the ubiquitin carboxy-terminal hydrolase L1 gene in Parkinson’s disease. Neurology 53:1858–1860
Miyake Y, Tanaka K, Fukushima W, Kiyohara C et al (2012) UCHL1 S18Y variant is a risk factor for Parkinson’s disease in Japan. BMC Neurol 62:1186–1471
Wang J, Zhao CY, Si YM (2002) ACT and UCH-L1 polymorphisms in Parkinson’s disease and age of onset. Mov Disord 17:767–771
Mizuta I, Satake W, Nakabayashi Y (2006) Multiple candidate gene analysis identifies alpha-synuclein as a susceptibility gene for sporadic Parkinson’s disease. Hum Mol Genet 15:1151–1158
Momose Y, Murata M, Kobayashi K (2002) Association studies of multiple candidate genes for Parkinson’s disease using single nucleotide polymorphisms. Ann Neurol 51:133–136
Tan EK, Puong KY, Fook-Chong S (2006) Case-control study of UCHL1S18Y variant in Parkinson’s disease. Mov Disord 21:1765–1768
Zhang ZJ, Burgunder JM, An XK, Wu Y et al (2008) Lack of evidence for association of a UCH-L1 S18Y polymorphism with Parkinson’s disease in a Han-Chinese population. Neurosci Lett 442:200–202
Satoh J, Kuroda Y (2001) A polymorphic variation of serine to tyrosine at codon 18 in the ubiquitin C-terminal hydrolase-L1 gene is associated with a reduced risk of sporadic Parkinson’s disease in a Japanese population. J Neurol Sci 189:13–17
Wu YR, Chen CM, Chen YC, Chao CY et al (2010) Ubiquitin specific proteases USP24 and USP40 and ubiquitin thiolesterase UCHL1 polymorphisms have synergic effect on the risk of Parkinson’s disease among Taiwanese. Clin Chim Acta 411:955–958
Wang L, Guo JF, Nie LL, Luo L et al (2011) Case–control study of the UCH-L1 S18Y variant in sporadic Parkinson’s disease in the Chinese population. J Clin Neurosci 18:541–544
Snapinn KW, Larson EB, Kawakami H, Ujike H et al (2011) The UCHL1 S18Y polymorphism and Parkinson’s disease in a Japanese population. Parkinsonism Relat Disord 17:473–475
Zhang J, Hattori N, Leroy E, Morris HR et al (2000) Association between a poly- morphism of ubiquitin carboxy-terminal hydrolase L1 (UCH-L1) gene and sporadic Parkinson’s disease. Parkinsonism Relat Disord 6:195–197
Tan EK, Lu CS, Peng R, Teo YY et al (2010) Analysis of the UCHL1 genetic variant in Parkinson’s disease among Chinese. Neurobiol Aging 31:2194–2196
Healy DG, Abou-Sleiman PM, Casas JP et al (2006) UCHL-1 is not a Parkinson’s disease susceptibility gene. Ann Neurol 59:627–633
Maraganore DM, Lesnick TG, Elbaz A et al (2004) UCHL1 is a Parkinson’s disease susceptibility gene. Ann Neurol 55:512–521
Ragland M, Hutter C, Zabetian C, Edwards K (2009) Association between the ubiquitin esterase L1 gene (UCHL1) S18Y variant and Parkinson’s Disease: a HuGE review and meta-analysis. Am J Epidemiol 170:1344–1357
Higgins JP, Thompson SG (2002) Quantifying heterogeneity in a meta-analysis. Stat Med 21:1539–1558
Zintzaras E, Ioannidis JP (2005) Heterogeneity testing in meta-analysis of genome searches. Genet Epidemiol 28:123–137
Mantel N, Haenszel W (1959) Statistical aspects of the analysis of data from retrospective studies of disease. J Natl Cancer Inst 22:719–748
DerSimonian R, Laird NM (1986) Meta-analysis in clinical trials. Control Clin Trials 7:177–188
Peters JL, Sutton AJ, Jones DR, Abrams KR, Rushton L (2006) Comparison of two methods to detect publication bias in meta-analysis. JAMA 295:676–680
Toda T, Momose Y, Murata M, Tamiya G et al (2003) Toward identification of susceptibility genes for sporadic Parkinson’s disease. J Neurol 250:III40–III43
Thacker EL, Ascherio A (2008) Familial aggregation of Parkinson’s disease: a meta-analysis. Mov Disord 23:1174–1183
Xiromerisiou G, Kyratzi E, Dardiotis E et al (2011) Lack of association of the UCHL-1 gene with Parkinson’s disease in a Greek cohort: a haplotype-tagging approach. Mov Disord 26:1955–1957
Anna Göbel BS, Eric A, Macklin PhD, Susen Winkler BS et al (2012) Genetic risk factors in Parkinson disease: Single gene effects and interactions of genotypes. J Neurol 259:2503–2505
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Sun, S., Zhao, Y., Jin, G. et al. Lack of association between UCHL1 S18Y gene polymorphism and Parkinson’s disease in the Asian population: a meta-analysis. Neurol Sci 35, 1867–1876 (2014). https://doi.org/10.1007/s10072-014-1973-4
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DOI: https://doi.org/10.1007/s10072-014-1973-4