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PMID: 15689450 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Functional interaction between APOE4 and LDL receptor isoforms in Alzheimer's disease.

Journal of medical genetics ·Vol. 42 ·No. 2 ·2005-02-00 ·Pages 129-31

Cheng D, Huang R, Lanham IS, Cathcart HM, Howard M, Corder EH, Poduslo SE

Abstract

Multiple genes have been provisionally associated with Alzheimer's disease, including the coding polymorphisms in exons 8 and 13 in the low density lipoprotein receptor gene (LDLR), situated on chromosome 19p13.2. The sample groups consisted of 180 AD patients and 141 control spouses. We carried out genotyping of LDLR8 and LDLR13. The LDLR8 GG genotype was common, found in 84% of the unaffected control subjects and 91% of the AD patients in our study. There was a ninefold elevation in risk associated with GG:CC versus A- and T- among APOE4+ subjects when compared with APOE4- subjects (odds ratio 9.3; 95% confidence interval 1.8 to 48.2). With the additional information on LDLR polymorphism, we defined an overall 12 fold elevation in risk for APOE4 in combination with LDLR GG:CC (11.9; 2.8 to 50.0; Fisher's exact test, p = 0.0002; standard power 0.999), compared with other subjects lacking all three of these polymorphisms. These results imply a functional interaction between ApoE and LDL receptor proteins that determines risk for Alzheimer's disease.

MeSH Terms

Aged Aged, 80 and over Alzheimer Disease/genetics Apolipoprotein E4 Apolipoproteins E/genetics Female Genetic Predisposition to Disease Genotype Humans Male Middle Aged Polymorphism, Genetic Protein Isoforms/genetics Receptors, LDL/genetics

Chemicals

Apolipoprotein E4 Apolipoproteins E Protein Isoforms Receptors, LDL

Authors & Affiliations

7 authors, click to expand affiliations / ORCID

Cheng D

Institute of Molecular Medicine and Genetics, Medical College of Georgia, Augusta, GA 30912, USA.

Huang R

Lanham I S

Cathcart H M

Howard M

Corder E H

Poduslo S E

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Article Info

Journal

Journal of medical genetics

Abbr.

J Med Genet

ISSN

1468-6244

DOI

10.1136/jmg.2004.024968

Published

2005-02-00

Pages

129-31

Language

English

Region

England

NLM ID

2985087R

PMCID

PMC1735987

Subset

Grants

NIA NIH HHS · U24 AG021886 · United States

NIA NIH HHS · U24AG21886 · United States

External Links

PubMed source DOI: 10.1136/jmg.2004.024968 PMC Full Text View journal details

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Functional interaction between APOE4 and LDL receptor isoforms in Alzheimer's disease.

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