HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Figures Only Full Text Full Text (PDF) Correspondence: Submit a response Alert me when this article is cited Alert me when Correspondence are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Mui, S. Articles by Hyman, B. T. Search for Related Content PubMed PubMed Citation Articles by Mui, S. Articles by Hyman, B. T.

A newly identified polymorphism in the apolipoprotein E enhancer gene region is associated with Alzheimer's disease and strongly with the epsilon 4 allele

From the Neurology Service (Drs. Gomez-Isla, Rebeck, and Hyman and Ms. Mui and Briggs), Massachusetts General Hospital, Boston, MA; and the Department of Preventive Medicine and Biostatistics (Dr. Wallace), University of Iowa College of Medicine, Iowa City, IA.
Supported by National Institutes of Health grants AG12406, AG05134, AG01206, AG10127, and a grant from the American Federation for Aging Research.
Received October 26, 1995. Accepted in final form January 5, 1996.
Address correspondence and reprint requests to Dr. Bradley T. Hyman, Neurology Service, Massachusetts General Hospital, Boston, MA 02114.

Apolipoprotein E allele 4 (apoE epsilon 4) is a major risk factor for late-onset AD. Inheritance of this allele is associated with an earlier age of onset of dementia in individuals with AD. It is unknown whether other polymorphisms in the apoE gene may influence the effect of apoE epsilon 4 on AD. We screened portions of the promoter enhancer element and of the apoE receptor binding domain for other polymorphisms that could affect risk of AD. In particular, a C/G polymorphism at position +113 of the apoE mRNA in the apoE intron 1 enhancer element (IE1) has been recently identified. We found no other polymorphisms. We studied the relationship of the two alleles of the IE1 polymorphism with AD and found an apparent association between IE1 G and AD (n = 94; p = 0.0515). However, the IE1 G allele is also closely associated with apoE epsilon 4 (p < 0.0001). When the presence of apoE epsilon 4 is covaried, the association between the IE1 G allele and AD is no longer statistically significant (odds ratio = 1.29, 95% confidence interval: 0.44, 3.78). In contrast, epsilon 4 is still highly associated with AD when IE1 G is controlled for (odds ratio = 5.91, 95% confidence interval: 3.29, 10.63). Furthermore, there is no significant association between the age of onset of dementia and the inheritance of the G allele. We believe that the apparent association between IE1 G and AD is a consequence of the association between the epsilon 4 and IE1 G alleles.

NEUROLOGY 1996;47: 196-201

This article has been cited by other articles:

				O. Belbin, J. L. Dunn, Y. Ling, L. Morgan, S. Chappell, H. Beaumont, D. Warden, D. A. Smith, N. Kalsheker, and K. Morgan Regulatory region single nucleotide polymorphisms of the apolipoprotein E gene and the rate of cognitive decline in Alzheimer's disease Hum. Mol. Genet., September 15, 2007; 16(18): 2199 - 2208. [Abstract] [Full Text] [PDF]

				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]

				W. Koch, J. Mehilli, A. Pfeufer, A. Schomig, and A. Kastrati Apolipoprotein E gene polymorphisms and thrombosis and restenosis after coronary artery stenting J. Lipid Res., December 1, 2004; 45(12): 2221 - 2226. [Abstract] [Full Text] [PDF]

				Z. Guo, L. Fratiglioni, M. Viitanen, L. Lannfelt, H. Basun, J. Fastbom, and B. Winblad Apolipoprotein E Genotypes and the Incidence of Alzheimer's Disease among Persons Aged 75 Years and Older: Variation by Use of Antihypertensive Medication? Am. J. Epidemiol., February 1, 2001; 153(3): 225 - 231. [Abstract] [Full Text] [PDF]

				J. Theuns and C. Van Broeckhoven Transcriptional regulation of Alzheimer's disease genes: implications for susceptibility Hum. Mol. Genet., October 1, 2000; 9(16): 2383 - 2394. [Abstract] [Full Text] [PDF]

				D. A. Nickerson, S. L. Taylor, S. M. Fullerton, K. M. Weiss, A. G. Clark, J. H. Stengård, V. Salomaa, E. Boerwinkle, and C. F. Sing Sequence Diversity and Large-Scale Typing of SNPs in the Human Apolipoprotein E Gene Genome Res., October 1, 2000; 10(10): 1532 - 1545. [Abstract] [Full Text]

				I. Tesseur, J. Van Dorpe, K. Spittaels, C. Van den Haute, D. Moechars, and F. Van Leuven Expression of Human Apolipoprotein E4 in Neurons Causes Hyperphosphorylation of Protein Tau in the Brains of Transgenic Mice Am. J. Pathol., March 1, 2000; 156(3): 951 - 964. [Abstract] [Full Text] [PDF]

				P. J. Harrison and P. W. J. Burnet The 5-HT2A (serotonin2A) receptor gene in the aetiology, pathophysiology and pharmacotherapy of schizophrenia J Psychopharmacol, January 1, 1997; 11(1): 18 - 20. [PDF]