Various deletions and point mutations in the Parkin gene have been strongly associated with Parkinson’s disease (PD) and parkinsonism, especially when the onset occurs at a young age. In this study, we screened 25 ‘early-onset’ (<49 years at onset) and 91 later-onset PD patients from a Han Chinese population from South-West China for deletions and mutations in the Parkin gene. We found no deletions or point mutations in exons 1–12 of the Parkin gene using direct sequence analysis and only detected the common Ser167Asn polymorphism. We analysed Ser167Asn in 116 patients with sporadic PD and 124 controls, matched for age and gender. There were significant differences in allele and genotype frequency between PD patients, with the 167Asn allele more common in cases than controls (46.6 vs. 35.1%; χ2 = 6.54, p = 0.011, odds ratio = 1.61, 95% confidence interval, CI, 1.10–2.37), as was the 167Asn genotype (17.3 vs. 11.3%; p = 0.04). The frequency of the 167Ser genotype was significantly lower in PD patients than in controls when compared with that of the other two genotypes combined (χ2 = 7.84, p = 0.005, odds ratio = 0.46, 95% CI 0.25 – 0.82). No significant differences in the frequencies of the allele and genotypes were found between patients classified into two groups according to symptoms at onset (χ2 = 0.191, p = 0.66, odds ratio = 1.12, 95% CI 0.65–1.95; χ2 = 0.24, p = 0.887) or age of onset (p = 0.787). In summary, homozygous deletion mutations and point mutations in exons 1–12 of the Parkin gene were not detected in this Han Chinese population, although we cannot exclude compound heterozygous deletions. In addition, our study suggests that the variant 167Asn increases the risk of developing PD.

Keywords:
Sporadic Parkinson’s disease, Parkin gene, Mutation, Polymorphism
1.
Kitada T, Asakawa S, Hattori N, Matsumine H, Yamamura Y, Minoshima S, et al: Mutations in the Parkin gene cause autosomal recessive juvenile parkinsonism. Nature 1998;392:605–608.
2.
Polymeropoulos MH, Lavedan C, Leroy E, Ide SE, Dehejia A, Dutra A, et al: Mutation in the alpha-synuclein gene identified in families with Parkinson’s disease. Science 1997;276:2045–2047.
3.
Leroy E, Boyer R, Auburger G, Leube B, Ulm G, Mezey E, et al: The ubiquitin pathway in Parkinson’s disease. Nature 1998;395:451–452.
4.
Giasson BI, Lee VM: Parkin and the molecular pathways of Parkinson’s disease. Neuron 2001;31:885–888.
5.
Kitada T, Asakawa S, Hattori N, Matsumine H, Yamamura Y, Minoshima S, et al: Mutations in the Parkin gene cause autosomal recessive juvenile parkinsonism. Nature 1998;392:605–608.
6.
Hattori N, Kitada T, Matsumine H, Asakawa S, Yamamura Y, Yoshino H, et al: Molecular genetic analysis of a novel Parkin gene in Japanese families with autosomal recessive juvenile parkinsonism: Evidence for variable homozygous deletions in the Parkin gene in affected individuals. Ann Neurol 1998;44:935–941.
7.
Lucking CB, Abbas N, Durr A, Bonifati V, Bonnet AM, de Broucker T, et al: Homozygous deletions in Parkin gene in European and North African families with autosomal recessive juvenile parkinsonism. The European Consortium on Genetic Susceptibility in Parkinson’s Disease and the French Parkinson’s Disease Genetics Study Group. Lancet 1998;352:1355–1356.
8.
Abbas N, Lucking CB, Ricard S, Durr A, Bonifati V, De Michele G, et al: A wide variety of mutations in the Parkin gene are responsible for autosomal recessive parkinsonism in Europe. French Parkinson’s Disease Genetics Study Group and the European Consortium on Genetic Susceptibility in Parkinson’s Disease. Hum Mol Genet 1999;8:567–574.
9.
Munoz E, Pastor P, Marti MJ, Oliva R, Tolosa E: A new mutation in the Parkin gene in a patient with atypical autosomal recessive juvenile parkinsonism. Neurosci Lett 2000;289:66–68.
10.
Alvarez V, Guisasola LM, Moreira VG, Lahoz CH, Coto E: Early-onset Parkinson’s disease associated with a new Parkin mutation in a Spanish family. Neurosci Lett 2001;313:108–110.
11.
Maruyama M, Ikeuchi T, Saito M, Ishikawa A, Yuasa T, Tanaka H, et al: Novel mutations, pseudo-dominant inheritance, and possible familial affects in patients with autosomal recessive juvenile parkinsonism. Ann Neurol 2000;48:245–250.
12.
Lucking CB, Durr A, Bonifati V, Vaughan J, De Michele G, Gasser T, et al: Association between early-onset Parkinson’s disease and mutations in the Parkin gene. French Parkinson’s Disease Genetics Study Group. N Engl J Med 2000;342:1560–1567.
13.
Terreni L, Calabrese E, Calella AM, Forloni G, Mariani C: New mutation (R42P) of the Parkin gene in the ubiquitin-like domain associated with parkinsonism. Neurology 2001;56:463–466.
14.
Kuroda Y, Mitsui T, Akaike M, Azuma H, Matsumoto T: Homozygous deletion mutation of the Parkin gene in patients with atypical parkinsonism. J Neurol Neurosurg Psychiatry 2001;71:231–234.
15.
Kobayashi T, Wang M, Hattori N, Matsumine H, Kondo T, Mizuno Y: Exonic deletion mutations of the Parkin gene among sporadic patients with Parkinson’s disease. Parkinsonism Relat Disord 2000;6:129–131.
16.
Hedrich K, Kann M, Lanthaler AJ, Dalski A, Eskelson C, Landt O, et al: The importance of gene dosage studies: Mutational analysis of the Parkin gene in early-onset parkinsonism. Hum Mol Genet 2001;10:1649–1656.
17.
Vaughan JR, Davis MB, Wood NW: Genetics of parkinsonism: A review. Ann Hum Genet 2001;65(pt 2):111–126.
18.
Gasser T: Genetics of Parkinson’s disease. J Neurol 2001;248:833–840.
19.
Hilker R, Klein C, Ghaemi M, Kis B, Strotmann T, Ozelius LJ, et al: Positron emission tomographic analysis of the nigrostriatal dopaminergic system in familial parkinsonism associated with mutations in the Parkin gene. Ann Neurol 2001;49:367–376.
20.
Jeon BS, Kim JM, Lee DS, Hattori N, Mizuno Y: An apparently sporadic case with Parkin gene mutation in a Korean woman. Arch Neurol 2001;58:988–989.
21.
Oliveri RL, Zappia M, Annesi G, Annesi F, Spadafora P, Pasqua AA, et al: The Parkin gene is not a major susceptibility locus for typical late-onset Parkinson’s disease. Neurol Sci 2001;22:73–74.
22.
Ujike H, Yamamoto M, Kanzaki A, Okumura K, Takaki M, Kuroda S: Prevalence of homozygous deletions of the Parkin gene in a cohort of patients with sporadic and familial Parkinson’s disease. Mov Disord 2001;16:111–113.
23.
Satoh J, Kuroda Y: Association of codon 167 Ser/Asn heterozygosity in the Parkin gene with sporadic Parkinson’s disease. Neuroreport 1999;10:2735–2739.
24.
Wang M, Hattori N, Matsumine H, Kobayashi T, Yoshino H, Morioka A, et al: Polymorphism in the Parkin gene in sporadic Parkinson’s disease. Ann Neurol 1999;45:655–658.
25.
Hu CJ, Sung SM, Liu HC, Lee CC, Tsai CH, Chang JG: Polymorphisms of the Parkin gene in sporadic Parkinson’s disease among Chinese in Taiwan. Eur Neurol 2000;44:90–93.
26.
Oliveri RL, Zappia M, Annesi G, Bosco D, Annesi F, Spadafora P, et al: The Parkin gene is not involved in late-onset Parkinson’s disease. Neurology 2001;57:359–362.
© 2003 S. Karger AG, Basel
2003
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.