Association of Genes Involved in the Metabolic Pathways of Amyloid-β and Tau Proteins With Sporadic Late-Onset Alzheimer's Disease in the Southern Han Chinese Population.
Association of Genes Involved in the Metabolic Pathways of Amyloid-β and Tau Proteins With Sporadic Late-Onset Alzheimer's Disease in the Southern Han Chinese Population.
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DOI：
10.3389/fnagi.2020.584801
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发表时间：
2020
影响因子：
4.8
通讯作者：
Shen L
中科院分区：
文献类型：
--
作者：
Xiao X;Jiao B;Liao X;Zhang W;Yuan Z;Guo L;Wang X;Zhou L;Liu X;Yan X;Tang B;Shen L
β淀粉样蛋白（Aβ）和tau蛋白代谢途径中的相关基因对阿尔茨海默病（AD）的发病有重要影响。各种研究已经探索了这些基因中的一些与高加索人群中的AD之间的关联;然而，关于这些关联的研究在中国人群中仍然有限。为了系统地评价这些基因与AD的关联，我们基于使用PubMed数据库选择的先前研究，研究了参与Aβ和tau代谢的19个基因。这项研究包括372例散发性迟发性AD（sLOAD）患者和345名来自中国南方的认知健康个体。这一结果在国际阿尔茨海默病基因组学项目（IGAP）中得到了复制。使用STRING v11数据库确定蛋白质-蛋白质相互作用。我们发现，在调整年龄、性别和APOE ε4状态并进行Bonferroni校正后，BIN 1的单核苷酸多态性rs 11682128赋予了sLOAD的易感性{校正P = 0.000153，比值比（OR）[95%置信区间（CI）] = 1.403（1.079-1.824）}，这在IGAP中得到了重复。蛋白质相互作用表明BIN 1与MAPT相关。此外，NEP和FERMT 2的罕见变体（0.0026 <校正P < 0.05）以及Aβ降解、tau病理学和tau磷酸酶途径（0.01 <校正P < 0.05）与sLOAD名义上显著相关。本研究提示，Aβ和tau代谢途径相关基因参与了中国南方汉族人群sLOAD的发病。
The genes involved in the metabolic pathways of amyloid-β (Aβ) and tau proteins significantly influence the etiology of Alzheimer’s disease (AD). Various studies have explored the associations between some of these genes and AD in the Caucasian population; however, researches regarding these associations remain limited in the Chinese population. To systematically evaluate the associations of these genes with AD, we investigated 19 genes involved in the metabolism of Aβ and tau based on previous studies selected using the PubMed database. This study included 372 patients with sporadic late-onset AD (sLOAD) and 345 cognitively healthy individuals from southern China. The results were replicated in the International Genomics of Alzheimer’s Project (IGAP). Protein–protein interactions were determined using the STRING v11 database. We found that a single-nucleotide polymorphism, rs11682128, of BIN1 conferred susceptibility to sLOAD after adjusting for age, sex, and APOE ε4 status and performing the Bonferroni correction {corrected P = 0.000153, odds ratio (OR) [95% confidence interval (CI)] = 1.403 (1.079–1.824)}, which was replicated in the IGAP. Protein–protein interactions indicated that BIN1 was correlated with MAPT. Moreover, rare variants of NEP and FERMT2 (0.0026 < corrected P < 0.05), and the Aβ degradation, tau pathology, and tau phosphatase pathways (0.01 < corrected P < 0.05), were nominally significantly associated with sLOAD. This study suggested that the genes involved in the metabolic pathways of Aβ and tau contributed to the etiology of sLOAD in the southern Han Chinese population.
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影响因子：
16.6
作者：
Franzmeier, Nicolai;Rubinski, Anna;Simpson, Donna M.
通讯作者：
Simpson, Donna M.
影响因子：
4.3
作者：
Kametani F;Hasegawa M
通讯作者：
Hasegawa M
影响因子：
30.8
作者：
Ionita-Laza I;McCallum K;Xu B;Buxbaum JD
通讯作者：
Buxbaum JD
DOI：
10.1016/j.jalz.2017.08.013
发表时间：
2018-03
期刊：
Alzheimer's & dementia : the journal of the Alzheimer's Association
影响因子：
--
作者：
Cruchaga C;Del-Aguila JL;Saef B;Black K;Fernandez MV;Budde J;Ibanez L;Deming Y;Kapoor M;Tosto G;Mayeux RP;Holtzman DM;Fagan AM;Morris JC;Bateman RJ;Goate AM;Dominantly Inherited Alzheimer Network (DIAN);Disease Neuroimaging Initiative (ADNI);NIA-LOAD family study;Harari O
通讯作者：
Harari O
影响因子：
11
作者：
Chapuis, J.;Hansmannel, F.;Gistelinck, M.;Mounier, A.;Van Cauwenberghe, C.;Kolen, K. V.;Geller, F.;Sottejeau, Y.;Harold, D.;Dourlen, P.;Grenier-Boley, B.;Kamatani, Y.;Delepine, B.;Demiautte, F.;Zelenika, D.;Zommer, N.;Hamdane, M.;Bellenguez, C.;Dartigues, J-F;Hauw, J-J;Letronne, F.;Ayral, A-M;Sleegers, K.;Schellens, A.;Broeck, L. V.;Engelborghs, S.;De Deyn, P. P.;Vandenberghe, R.;O'Donovan, M.;Owen, M.;Epelbaum, J.;Mercken, M.;Karran, E.;Bantscheff, M.;Drewes, G.;Joberty, G.;Campion, D.;Octave, J-N;Berr, C.;Lathrop, M.;Callaerts, P.;Mann, D.;Williams, J.;Buee, L.;Dewachter, I.;Van Broeckhoven, C.;Amouyel, P.;Moechars, D.;Dermaut, B.;Lambert, J-C
通讯作者：
Lambert, J-C