Department of Neurology, Affiliated Hospital of Guangdong Medical College, 524001, Zhanjiang, China.
J Neural Transm (Vienna). 2010 Jan;117(1):97-104. doi: 10.1007/s00702-009-0334-6. Epub 2009 Nov 10.
The receptor for advanced glycation end products (RAGE) is associated with several pathological states including Alzheimer's disease (AD) pathology, while its soluble form (sRAGE) acts as a decoy receptor. We have tested for association of AD with a functional single-nucleotide polymorphism (SNP) in the RAGE gene (G82S; rs2070600), a SNP associated with increased ligand affinity of RAGE. Analysis of a Chinese cohort (276 cases; 254 controls) showed a higher prevalence of the RAGE 82S allele and GS + SS genotype in the patients [82S vs. 82G: P = 0.017, odds ratio (OR) = 1.431; GS + SS vs. GG: P = 0.025, OR = 1.490]. Further stratification analysis revealed that the association of the RAGE G82S polymorphism with AD was significant in early onset AD stratum. Moreover, plasma sRAGE levels were lower in AD than in normal elderly controls, and the presence of the risk allele was associated with further plasma sRAGE reduction and a fast cognitive deterioration. The present study provides preliminary evidence that the RAGE G82S variant is involved in genetic susceptibility to AD.
晚期糖基化终产物受体（RAGE）与多种病理状态相关，包括阿尔茨海默病（AD）病理，而其可溶性形式（sRAGE）则作为诱饵受体。我们已经测试了 AD 与 RAGE 基因中的一个功能性单核苷酸多态性（SNP）（G82S；rs2070600）之间的关联，该 SNP 与 RAGE 的配体亲和力增加有关。对中国队列（276 例病例；254 例对照）的分析表明，患者中 RAGE 82S 等位基因和 GS + SS 基因型的患病率更高[82S 与 82G：P = 0.017，优势比（OR）= 1.431；GS + SS 与 GG：P = 0.025，OR = 1.490]。进一步的分层分析显示，RAGE G82S 多态性与 AD 的关联在早发性 AD 分层中具有统计学意义。此外，AD 患者的血浆 sRAGE 水平低于正常老年对照组，风险等位基因的存在与进一步降低血浆 sRAGE 水平和认知功能迅速恶化有关。本研究初步证据表明，RAGE G82S 变体与 AD 的遗传易感性有关。
