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Int J Geriatr Psychiatry. 2017 Dec;32(12):1241-1246. doi: 10.1002/gps.4600. Epub 2016 Oct 4.

Genetic association between RAGE polymorphisms and Alzheimer's disease and Lewy body dementias in a Japanese cohort: a case-control study.

Author information

1
Department of Psychiatry, Juntendo University School of Medicine, Tokyo, Japan.
2
Department of Psychiatry, Jikei University School of Medicine, Tokyo, Japan.
3
Division of Molecular Genetics, Institute of DNA Medicine, Jikei University School of Medicine, Tokyo, Japan.
4
Department of Neurology, Juntendo University School of Medicine, Tokyo, Japan.

Abstract

BACKGROUND/AIMS:

Interaction of receptor for advanced glycation end products (RAGE) with amyloid-β increases amplification of oxidative stress and plays pathological roles in Alzheimer's disease (AD). Oxidative stress leads to α-synuclein aggregation and is also a major contributing factor in the pathogenesis of Lewy body dementias (LBDs). Therefore, we aimed to investigate whether RAGE gene polymorphisms were associated with AD and LBDs.

METHODS:

Four single nucleotide polymorphisms (SNPs)-rs1800624, rs1800625, rs184003, and rs2070600-of the gene were analyzed using a case-control study design comprising 288 AD patients, 76 LBDs patients, and 105 age-matched controls.

RESULTS:

Linkage disequilibrium (LD) examination showed strong LD from rs1800624 to rs2070600 on the gene (1.1 kb) in our cases in Japan. Rs184003 was associated with an increased risk of AD. Although there were no statistical associations for the other three SNPs, haplotypic analyses detected genetic associations between AD and the RAGE gene. Although relatively few cases were studied, results from the SNPs showed that they did not modify the risk of developing LBDs in the Japanese population.

CONCLUSION:

Our findings suggested that polymorphisms in the RAGE gene are involved in genetic susceptibility to AD. Copyright © 2016 John Wiley & Sons, Ltd.

KEYWORDS:

Alzheimer's disease; Lewy body dementias; apolipoprotein E; polymorphism; receptor for advanced glycation end-products (RAGE)

PMID:
27699858
DOI:
10.1002/gps.4600
[Indexed for MEDLINE]

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