Genetic association of low density lipoprotein receptor and Alzheimer's disease.

TitleGenetic association of low density lipoprotein receptor and Alzheimer's disease.
Publication TypeJournal Article
Year of Publication2005
AuthorsGopalraj RK, Zhu H, Kelly JF, Mendiondo M, Pulliam JF, Bennett DA, Estus S
JournalNeurobiol Aging
Volume26
Issue1
Pagination1-7
Date Published2005 Jan
ISSN0197-4580
KeywordsAged, Aged, 80 and over, Alleles, Alzheimer Disease, Case-Control Studies, Exons, Female, Gene Frequency, Genetic Linkage, Genetic Variation, Genotype, Humans, Male, Polymorphism, Single Nucleotide, Receptors, LDL
Abstract

The low density lipoprotein receptor (LDLR) is an attractive candidate gene for genetic association with Alzheimer's disease (AD) because: (i) the LDLR is an apolipoprotein E (apoE) receptor, alleles of which have been associated with AD, (ii) LDLR resides at chromosome 19p13.3 within a region linked to AD, and (iii) LDLR modulates the homeostasis of cholesterol, which itself appears associated with AD. Therefore, we evaluated whether LDLR haplotypes alter the odds of AD by performing an association study examining three LDLR single nucleotide polymorphisms (SNPs) in 118 AD patients and 133 non-AD subjects. LDLR genotypes were obtained by TaqMan allelic discrimination assays. Although individual LDLR SNPs were not associated with AD, analyses of unambiguous haplotypes suggested the hypothesis that the 211 LDLR haplotype was associated with reduced odds of AD. We then evaluated this hypothesis in a second study cohort, i.e., the Religious Orders Study. These results supported the hypothesis that the 211 LDLR haplotype is associated with reduced odds of AD. Moreover, these data suggested further associations between LDLR variants and AD. Thus, LDLR variants appear significantly associated with AD and merit additional study.

DOI10.1016/j.neurobiolaging.2004.09.001
Alternate JournalNeurobiol. Aging
PubMed ID15585340
Grant List2P50AG05144-17 / AG / NIA NIH HHS / United States
P30AG10161 / AG / NIA NIH HHS / United States
R01AG15819 / AG / NIA NIH HHS / United States
R01AG21362 / AG / NIA NIH HHS / United States
R01AG21545 / AG / NIA NIH HHS / United States