Neurology
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Correspondence:
Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when Correspondence are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Lambert, J. C.
Right arrow Articles by Chartier-Harlin, M. C.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Lambert, J. C.
Right arrow Articles by Chartier-Harlin, M. C.
Related Collections
Right arrow Alzheimer's disease
Right arrow All epidemiology
Right arrow Risk factors in epidemiology
Right arrow All Genetics
Right arrow Association studies in genetics

Neurology 2002;59:59-66
© 2002 American Academy of Neurology

Contribution of APOE promoter polymorphisms to Alzheimer’s disease risk

J. C. Lambert, PhD, L. Araria-Goumidi, BSc, L. Myllykangas, MD, C. Ellis, BSc, J. C. Wang, PhD, M. J. Bullido, PhD, J. M. Harris, BSc, M. J. Artiga, PhD, D. Hernandez, BSc, J. M. Kwon, MD, B. Frigard, MD, R. C. Petersen, MD, PhD, A. M. Cumming, PhD, F. Pasquier, MD, PhD, I. Sastre, BSc, P. J. Tienari, MD, PhD, A. Frank, MD, R. Sulkava, MD, PhD, J. C. Morris, MD, D. St. Clair, MD, D. M. Mann, PhD, F. Wavrant-DeVrièze, PhD, M. Ezquerra-Trabalon, PhD, P. Amouyel, MD, PhD, J. Hardy, PhD, M. Haltia, MD, PhD, F. Valdivieso, PhD, A. M. Goate, PhD, J. Pérez-Tur, PhD, C. L. Lendon, PhD and M. C. Chartier-Harlin, PhD

From the INSERM U508 (Drs. Lambert, Ezquerra-Trabalon, Amouyel, and Chartier-Harlin, and L. Araria-Goumidi), Institut Pasteur de Lille, Lille, France; Molecular Psychiatry Department (Drs. Lambert and Lendon and J. Harris), Division of Neuroscience, Queen Elisabeth Psychiatry Hospital, University of Birmingham, United Kingdom; Department of Pathology (Drs. Myllykangas and Haltia), University of Helsinki and Helsinki University Central Hospital, Finland; Department of Neuroscience (C. Ellis, D. Hernandez, and Drs. Wavrant-DeVrièze, Hardy, and Pérez-Tur), Mayo Clinic, Jacksonville, FL; Departments of Psychiatry (Drs. Wang and Goate) and Neurology (Drs. Kwon and Morris), Washington University School of Medicine, St. Louis, MO; Departamento de Biologia Molecular (Drs. Bullido, Artiga, and Valdivieso and I. Sastre) and Centro de Biologia Molecular Severo Ochoa (CSIC-UAM), Cantoblanco, Madrid, Spain; Centre de Gériatrie de Wasquehal-Molinel (Dr. Frigard), Wasquehal, France; Department of Neurology (Dr. Petersen), Mayo Clinic, Rochester, MN; Department of Molecular and Cell Biology (Drs. Cumming and Pérez-Tur), University of Aberdeen, United Kingdom; CHR et Université de Lille (Dr. Pasquier), Clinique Neurologique, Centre de la Mémoire, Hôpital Salengro, Lille, France; Department of Neurology (Dr. Tienari), Helsinki University Central Hospital, Finland; Servicio de Neurologia (Dr. Frank), Hospital Universitario la PAZ (UAM), Madrid, Spain; Department of Public Health and General Practice (Dr. Sulkava), University of Kuopio, Finland; Greater Manchester Neurosciences Centre (Dr. St Clair), Hope Hospital, Salford, United Kingdom; Laboratory Medicine Academic Group (Dr. Mann), Department of Medicine, Stopford Building, University of Manchester, United Kingdom; Unitat de Genètica Molecular (Dr. Pérez-Tur), Institut de Biomedicina de València-CSIC, València, Spain.

Address correspondence and reprint requests to Dr. Marie-Christine Chartier-Harlin, Unite INSERM U508, Institut Pasteur de Lille, 1 rue du Professor Calmette, BP 245, 59019 Lille, Cédex, France; e-mail: marie-christine.chartier{at}pasteur-lille.fr

Objective: To determine whether the effects of APOE promoter polymorphisms on AD are independent of the APOE-{epsilon}4 allele.

Background: Recently, the -491 A->T and -219 G->T polymorphisms located in the APOE promoter have been suggested to be risk factors for AD. However, the effects of these polymorphisms have not always been reproduced in case-control studies, possibly because of the strong linkage disequilibrium existing at this locus or the characteristics of the populations studied.

Methods: Data collection was performed from six independent samples (1,732 patients with AD and 1,926 control subjects) genotyped for APOE exon 4 and the two APOE promoter polymorphisms. The risks associated with the APOE polymorphisms for developing AD were estimated using logistic regression procedures and calculation of odds ratios with 95% CI adjusted by age, sex, and collection center. Independence of the APOE promoter polymorphisms was tested by stratification for APOE-{epsilon}4 and tertile design was used for age stratification.

Results: The independence of the -491 AA genotype was observed in the whole sample whereas the independence of the -219 TT genotype was observed only in the oldest population.

Conclusion: The -491 and -219 APOE promoter polymorphisms incur risk for AD in addition to risk associated with the APOE-{epsilon}4 allele, with age accentuating the effect of the -219 TT genotype. Because these polymorphisms appear to influence apoE levels, these results suggest that APOE expression is an important determinant of AD pathogenesis.




This article has been cited by other articles:


Home page
 NeurologyHome page
P. van Vliet, R.G.J. Westendorp, P. Eikelenboom, H. C. Comijs, M. Frolich, E. Bakker, W. van der Flier, and E. van Exel
Parental history of Alzheimer disease associated with lower plasma apolipoprotein E levels
Neurology, September 1, 2009; 73(9): 681 - 687.
[Abstract] [Full Text] [PDF]

Home page
 Journals of Gerontology Series A: Biological Sciences and Medical SciencesHome page
D. C. Ewbank
Differences in the Association Between Apolipoprotein E Genotype and Mortality Across Populations
J. Gerontol. A Biol. Sci. Med. Sci., August 1, 2007; 62(8): 899 - 907.
[Abstract] [Full Text] [PDF]

Home page
 Br J AnaesthHome page
M. Wilson and H. Montgomery
Impact of genetic factors on outcome from brain injury
Br. J. Anaesth., July 1, 2007; 99(1): 43 - 48.
[Abstract] [Full Text] [PDF]

Home page
 Mult SclerHome page
B A Parmenter, D R Denney, S G Lynch, L S Middleton, and L M Harlan
Cognitive impairment in patients with multiple sclerosis: association with the APOE gene and promoter polymorphisms
Multiple Sclerosis, January 1, 2007; 13(1): 25 - 32.
[Abstract] [PDF]

Home page
 J. Neurol. Neurosurg. PsychiatryHome page
J-C Lambert, D Mann, F Richard, J Tian, J Shi, U Thaker, S Merrot, J Harris, B Frigard, T Iwatsubo, et al.
Is there a relation between APOE expression and brain amyloid load in Alzheimer's disease?
J. Neurol. Neurosurg. Psychiatry, July 1, 2005; 76(7): 928 - 933.
[Abstract] [Full Text] [PDF]

Home page
 Hum Mol GenetHome page
N. J. Bray, L. Jehu, V. Moskvina, J. D. Buxbaum, S. Dracheva, V. Haroutunian, J. Williams, P. R. Buckland, M. J. Owen, and M. C. O'Donovan
Allelic expression of APOE in human brain: effects of epsilon status and promoter haplotypes
Hum. Mol. Genet., November 15, 2004; 13(22): 2885 - 2892.
[Abstract] [Full Text] [PDF]

Home page
 J. Neurol. Neurosurg. PsychiatryHome page
E Arnaiz, O Almkvist, R J Ivnik, E G Tangalos, L O Wahlund, B Winblad, and R C Petersen
Mild cognitive impairment: a cross-national comparison
J. Neurol. Neurosurg. Psychiatry, September 1, 2004; 75(9): 1275 - 1280.
[Abstract] [Full Text] [PDF]

Home page
 Br J OphthalmolHome page
S Lake, E Liverani, M Desai, R Casson, B James, A Clark, and J F Salmon
Normal tension glaucoma is not associated with the common apolipoprotein E gene polymorphisms
Br J Ophthalmol, April 1, 2004; 88(4): 491 - 493.
[Abstract] [Full Text] [PDF]

Home page
 J. Neurol. Neurosurg. PsychiatryHome page
J-C Lambert, D Mann, J Harris, L Araria-Goumidi, M-C Chartier-Harlin, D Cottel, T Iwatsubo, P Amouyel, and C Lendon
Association study of Notch 4 polymorphisms with Alzheimer's disease
J. Neurol. Neurosurg. Psychiatry, March 1, 2004; 75(3): 377 - 381.
[Abstract] [Full Text] [PDF]

Home page
 J. Med. Genet.Home page
J-C Lambert, N Coyle, and C Lendon
The allelic modulation of apolipoprotein E expression by oestrogen: potential relevance for Alzheimer's disease
J. Med. Genet., February 1, 2004; 41(2): 104 - 112.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Cell. Biol.Home page
M. A. Christensen, W. Zhou, H. Qing, A. Lehman, S. Philipsen, and W. Song
Transcriptional Regulation of BACE1, the {beta}-Amyloid Precursor Protein {beta}-Secretase, by Sp1
Mol. Cell. Biol., January 15, 2004; 24(2): 865 - 874.
[Abstract] [Full Text] [PDF]

Home page
 NeurologyHome page
C. L. Lendon, J. M. Harris, A. L. Pritchard, J. A.R. Nicoll, G. M. Teasdale, and G. Murray
Genetic variation of the APOE promoter and outcome after head injury
Neurology, September 9, 2003; 61(5): 683 - 685.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Copyright © 2002 by AAN Enterprises, Inc.