Genetic association between RAGE polymorphisms and Alzheimer's disease and Lewy body dementias in a Japanese cohort: a case-control study.
Genetic association between RAGE polymorphisms and Alzheimer's disease and Lewy body dementias in a Japanese cohort: a case-control study.
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日本队列中 RAGE 多态性与阿尔茨海默病和路易体痴呆之间的遗传关联：病例对照研究。
DOI：
10.1002/gps.4600
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发表时间：
2016
影响因子：
4
通讯作者：
Arai H.
中科院分区：
文献类型：
--
作者：
Takeshita Y;Shibata N;Kasanuki K;Nagata T;Shinagawa S;Kobayashi N;Ohnuma T;Suzuki A;Kawai E;Takayama T;Nishioka K;Motoi Y;Hattori N;Nakayama K;Yamada H;Arai H.
背景/目的晚期糖基化终末产物受体（receptor for advanced glycation end products，AGEs）与β淀粉样蛋白的相互作用增加了氧化应激的放大，并在阿尔茨海默病（Alzheimer's disease，AD）中发挥病理作用。氧化应激导致α-突触核蛋白聚集，也是路易体痴呆（LBD）发病机制的主要促成因素。方法采用病例-对照研究设计，对288例AD患者、76例LBD患者、100例正常对照和100例正常对照的RAGE基因的rs 1800624、rs 1800625、rs 184003和rs 2070600 4个单核苷酸多态性（SNPs）进行分析，结果连锁不平衡（LD）检查显示，我们在日本的病例中，基因（1.1 kb）上从rs 1800624到rs 2070600存在较强的LD。Rs 184003与AD风险增加相关。虽然其他三个SNPs没有统计学关联，但单倍型分析检测到AD和theRAGE基因之间的遗传关联。虽然相对较少的情况下进行了研究，从SNPs的结果表明，他们没有修改的风险发展LBD在日本population.ConclusionOur研究结果表明，多态性在theRAGE基因参与遗传易感性AD。版权所有© 2016约翰威利父子有限公司.
Background/AimsInteraction 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 whetherRAGEgene polymorphisms were associated with AD and LBDs.MethodsFour 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.ResultsLinkage 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 theRAGEgene. 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.ConclusionOur findings suggested that polymorphisms in theRAGEgene are involved in genetic susceptibility to AD. Copyright © 2016 John Wiley & Sons, Ltd.