A polymorphism in the regulatory region of APOE associated with risk for Alzheimer's dementia

María Jesús Bullido; María Jesús Artiga; María Recuero; Isabel Sastre; Miguel Angel García; Jesús Aldudo; Corinne Lendon; Sang Woo Han; John C. Morris; Anna Frank; Jesús Vázquez; Alison Goate; Fernando Valdivieso

doi:10.1038/ng0198-69

A polymorphism in the regulatory region of APOE associated with risk for Alzheimer's dementia

María Jesús Bullido, María Jesús Artiga, María Recuero, Isabel Sastre, Miguel Angel García, Jesús Aldudo, Corinne Lendon, Sang Woo Han, John C. Morris, Anna Frank, Jesús Vázquez, Alison Goate, Fernando Valdivieso

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Abstract

The ε4 allele of the apolipoprotein E gene (APOE) has been associated with an increased risk of developing Alzheimer's disease (AD; refs 1,2). However, it is apparent that the APOEε4 allele alone is neither necessary nor sufficient to cause the disease. We have recently found three new polymorphisms within the APOE transcriptional regulatory region (M.J.A. et al, manuscript submitted) and now establish an association between one of these polymorphisms (-491A/T) and dementia as observed in Alzheimer's disease, in two independent clinical populations. The results suggest that homozygosity of a common variant (-491A) is associated with increased risk for AD, and that this association is independent of APOEz4 status. In vitro studies suggest that the -491A/T polymorphism may increase risk for AD by altering the level of ApoE protein expression.

Original language	English
Pages (from-to)	69-71
Number of pages	3
Journal	Nature Genetics
Volume	18
Issue number	1
DOIs	https://doi.org/10.1038/ng0198-69
State	Published - 1998

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title = "A polymorphism in the regulatory region of APOE associated with risk for Alzheimer's dementia",

abstract = "The ε4 allele of the apolipoprotein E gene (APOE) has been associated with an increased risk of developing Alzheimer's disease (AD; refs 1,2). However, it is apparent that the APOEε4 allele alone is neither necessary nor sufficient to cause the disease. We have recently found three new polymorphisms within the APOE transcriptional regulatory region (M.J.A. et al, manuscript submitted) and now establish an association between one of these polymorphisms (-491A/T) and dementia as observed in Alzheimer's disease, in two independent clinical populations. The results suggest that homozygosity of a common variant (-491A) is associated with increased risk for AD, and that this association is independent of APOEz4 status. In vitro studies suggest that the -491A/T polymorphism may increase risk for AD by altering the level of ApoE protein expression.",

author = "Bullido, {Mar{\'i}a Jes{\'u}s} and Artiga, {Mar{\'i}a Jes{\'u}s} and Mar{\'i}a Recuero and Isabel Sastre and Garc{\'i}a, {Miguel Angel} and Jes{\'u}s Aldudo and Corinne Lendon and Han, {Sang Woo} and Morris, {John C.} and Anna Frank and Jes{\'u}s V{\'a}zquez and Alison Goate and Fernando Valdivieso",

year = "1998",

doi = "10.1038/ng0198-69",

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T1 - A polymorphism in the regulatory region of APOE associated with risk for Alzheimer's dementia

AU - Bullido, María Jesús

AU - Artiga, María Jesús

AU - Recuero, María

AU - Sastre, Isabel

AU - García, Miguel Angel

AU - Aldudo, Jesús

AU - Lendon, Corinne

AU - Han, Sang Woo

AU - Morris, John C.

AU - Frank, Anna

AU - Vázquez, Jesús

AU - Goate, Alison

AU - Valdivieso, Fernando

PY - 1998

Y1 - 1998

N2 - The ε4 allele of the apolipoprotein E gene (APOE) has been associated with an increased risk of developing Alzheimer's disease (AD; refs 1,2). However, it is apparent that the APOEε4 allele alone is neither necessary nor sufficient to cause the disease. We have recently found three new polymorphisms within the APOE transcriptional regulatory region (M.J.A. et al, manuscript submitted) and now establish an association between one of these polymorphisms (-491A/T) and dementia as observed in Alzheimer's disease, in two independent clinical populations. The results suggest that homozygosity of a common variant (-491A) is associated with increased risk for AD, and that this association is independent of APOEz4 status. In vitro studies suggest that the -491A/T polymorphism may increase risk for AD by altering the level of ApoE protein expression.

AB - The ε4 allele of the apolipoprotein E gene (APOE) has been associated with an increased risk of developing Alzheimer's disease (AD; refs 1,2). However, it is apparent that the APOEε4 allele alone is neither necessary nor sufficient to cause the disease. We have recently found three new polymorphisms within the APOE transcriptional regulatory region (M.J.A. et al, manuscript submitted) and now establish an association between one of these polymorphisms (-491A/T) and dementia as observed in Alzheimer's disease, in two independent clinical populations. The results suggest that homozygosity of a common variant (-491A) is associated with increased risk for AD, and that this association is independent of APOEz4 status. In vitro studies suggest that the -491A/T polymorphism may increase risk for AD by altering the level of ApoE protein expression.

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JO - Nature Genetics

JF - Nature Genetics

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A polymorphism in the regulatory region of APOE associated with risk for Alzheimer's dementia

Abstract

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