Journal Mobile Options
Table of Contents
Vol. 25, No. 4, 2008
Issue release date: April 2008

Analysis of UBQLN1 Variants in a Polish Alzheimer’s Disease Patient: Control Series

Golan M.P. · Melquist S. · Safranow K. · Styczyńska M. · Słowik A. · Kobryś M. · Żekanowski C. · Barcikowska M.
To view the fulltext, log in and/or choose pay-per-view option

Individual Users: Register with Karger Login Information

Please create your User ID & Password





Contact Information











I have read the Karger Terms and Conditions and agree.

To view the fulltext, please log in

To view the pdf, please log in

Abstract

Late-onset Alzheimer’s disease (LOAD) is the most common neurodegenerative disorder, and has a complex etiology. Recently an intronic polymorphism in the ubiquilin 1 gene (UBQLN1) and a particular haplotype was reported to be associated with LOAD. We investigated whether variants in UBQLN1 confer a risk for the disease in 407 Polish LOAD patients and 407 controls. We observed a weak association with the rs2781002 polymorphism, however, contrary to the initial reports, in our group the association was with the A allele. Risk estimation for AA versus GG genotypes showed that the AA genotype is a weak risk factor for AD (OR = 1.8, 95% CI = 1.1–3.1, p = 0.025). This effect was stronger in a group of LOAD patients without APOE4 allele. Haplotype analyses indicate that there is an increase of haplotypes with an A allele in the case group. Also, the specific haplotypes with the A allele that increase AD risk differ between the APOE4-positive and APOE4-negative pools. However, the association observed seems to be driven mostly by rare (<5%) haplotypes. Results suggest a need for additional association studies and in silico analysis of the UBQLN1 locus.



Copyright / Drug Dosage

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 or, in the case of photocopying, direct payment of a specified fee to the Copyright Clearance Center.
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 goverment 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.

References

  1. Zekanowski C, Religa D, Graff C, Filipek S, Kuznicki J: Genetic aspects of Alzheimer’s disease. Acta Neurobiol Exp (Wars) 2004;64:19–31.
  2. Finckh U: The future of genetic association studies in Alzheimer disease. J Neural Transm 2003;110:253–266.
  3. Blacker D, Bertram L, Saunders AJ, Moscarillo TJ, Albert MS, Wiener H, Perry RT, Collins JS, Harrell LE, Go RC, Mahoney A, Beaty T, Fallin MD, Avramopoulos D, Chase GA, Folstein MF, McInnis MG, Bassett SS, Doheny KJ, Pugh EW, Tanzi RE; NIMH Genetics Initiative Alzheimer’s Disease Study Group. Results of a high-resolution genome screen of 437 Alzheimer’s disease families. Hum Mol Genet 2003;12:23–32.
  4. Myers A, Wavrant De-Vrieze F, Holmans P, Hamshere M, Crook R, Compton D, Marshall H, Meyer D, Shears S, Booth J, Ramic D, Knowles H, Morris JC, Williams N, Norton N, Abraham R, Kehoe P, Williams H, Rudrasingham V, Rice F, Giles P, Tunstall N, Jones L, Lovestone S, Williams J, Owen MJ, Hardy J, Goate A: Full genome screen for Alzheimer disease: stage II analysis. Am J Med Genet 2002;114:235–244.
  5. Bertram L, Hiltunen M, Parkinson M, Ingelsson M, Lange C, Ramasamy K, Mullin K, Menon R, Sampson AJ, Hsiao MY, Elliott KJ, Velicelebi G, Moscarillo T, Hyman BT, Wagner SL, Becker KD, Blacker D, Tanzi RE: Family-based association between Alzheimer’s disease and variants in UBQLN1. N Engl J Med 2005;352:884–894.
  6. Kamboh MI, Minster RL, Feingold E, DeKosky ST: Genetic association of ubiquilin with Alzheimer’s disease and related quantitative measures. Mol Psychiatry 2006;11:273–279.
  7. Slifer MA, Martin ER, Bronson PG, Browning-Large C, Doraiswamy PM, Welsh-Bohmer KA, Gilbert JR, Haines JL, Pericak-Vance MA: Lack of association between UBQLN1 and Alzheimer disease. Am J Med Genet B Neuropsychiatr Genet 2006;141:208–213.
  8. Bensemain F, Chapuis J, Tian J, Shi J, Thaker U, Lendon C, Iwatsubo T, Amouyel P, Mann D, Lambert JC. Association study of the Ubiquilin gene with Alzheimer’s disease. Neurobiol Dis 2006;22:691–693.
  9. Smemo S, Nowotny P, Hinrichs AL, Kauwe JS, Cherny S, Erickson K, Myers AJ, Kaleem M, Marlowe L, Gibson AM, Hollingworth P, O’Donovan MC, Morris CM, Holmans P, Lovestone S, Morris JC, Thal L, Li Y, Grupe A, Hardy J, Owen MJ, Williams J, Goate A: Ubiquilin 1 polymorphisms are not associated with late-onset Alzheimer’s disease. Ann Neurol 2006;59:21–26.
  10. Brouwers N, Sleegers K, Engelborghs S, Bogaerts V, van Duijn CM, De Deyn PP, Van Broeckhoven C, Dermaut B: The UBQLN1 polymorphism, UBQ-8i, at 9q22 is not associated with Alzheimer’s disease with onset before 70 years. Neurosci Lett 2006;392:72–74.
  11. Arias-Vasquez A, de Lau L, Pardo L, Liu F, Feng BJ, Bertoli-Avella A, Isaacs A, Aulchenko Y, Hofman A, Oostra B, Breteler M, van Duijn C: Relationship of the ubiquilin 1 gene with Alzheimer’s and Parkinson’s disease and cognitive function. Neurosci Lett 2007;424:1–5.
  12. Styczynska M, Religa D, Pfeffer A, Luczywek E, Wasiak B, Styczynski G, Peplonska B, Gabryelewicz T, Golebiowski M, Kobrys M, Barcikowska M: Simultaneous analysis of five genetic risk factors in Polish patients with Alzheimer’s disease. Neurosci Lett 2003;344:99–102.
  13. McKhann G, Drachman D, Folstein M, Katzman R, Price D, Stadlan EM: Clinical diagnosis of Alzheimer’s disease: report of the NINCDS-ADRDA Work Group under the auspices of Department of Health and Human Services Task Force on Alzheimer’s Disease. Neurology 1984;34:939–944.
  14. Sasieni PD: From genotypes to genes: doubling the sample size. Biometrics 1997;53:1253–1261.
  15. Schaid DJ, Rowland CM, Tines DE, Jacobson RM, Poland GA: Score tests for association between traits and haplotypes when linkage phase is ambiguous. Am J Hum Genet 2002;70:425–434.
  16. Thomas AV, Herl L, Spoelgen R, Hiltunen M, Jones PB, Tanzi RE, Hyman BT, Berezovska O: Interaction between presenilin 1 and ubiquilin 1 as detected by fluorescence lifetime imaging microscopy and a high throughput fluorescent plate reader. J Biol Chem 2006;281:26400–26407.


Pay-per-View Options
Direct payment This item at the regular price: USD 38.00
Payment from account With a Karger Pay-per-View account (down payment USD 150) you profit from a special rate for this and other single items.
This item at the discounted price: USD 26.50