title: Meta-analysis of the Association between Alzheimer Disease and Variants in GAB2, PICALM, and SORL1.
abstract: The genetic variants play a crucial role in the pathogenesis of Alzheimer's disease (AD), while the relationships of specific single nucleotide polymorphisms (SNPs) with AD are still controversial. We performed the meta-analysis to obtain a more precise estimation of whether growth factor receptor-bound protein-associated binding protein 2 (GAB2), phosphatidylinositol binding clathrin assembly protein (PICALM), and sortilin-related receptor (SORL1) variants are associated with AD. Databases including PubMed, Embase, and Cochrane Library were searched to find relevant studies. Cochran's Q-statistic and I2were used to assess the heterogeneity among the included studies. Odds ratios (OR) and 95 % confidence intervals (95 % CIs) were conducted to evaluate the association between the SNP and the susceptibility to AD. Publication bias was estimated by funnel plots. All of the statistical analyses were implemented using R Version 3.2.1 software. A total of 35 case-control studies involving 15 SNPs were included. There was no significant association between SNPs of GAB2 rs2373115 (G > T) and PICALM rs541458 (C > T) and AD. The allele T of rs3851179 in PICALM was associated with a 13 % increase in the risk of AD. Seven SNPs on SORL1 were significantly associated with AD. Four SNPs, including rs1010159*T, rs641120*A, rs668387*T, and rs689021*A, were associated with a decreased risk of AD, while the other three SNPs, including rs12285364*T, rs2070045*G, and rs2282649*T, were all associated with an increased risk of AD. The results of the present study suggested that multiple gene variants were associated with AD. The SNP of rs3851179 (PICALM), rs12285364 (SORL1), rs2070045 (SORL1), and rs2282649 (SORL1) was associated with an increased risk of AD, whereas SORL1 rs1010159, rs641120, rs668387, and rs689021 were associated with a decreased risk of AD.
authors.affiliation: Emergency Department, Linyi People's Hospital, Linyi, 276003, Shandong, China.
authors.forename: Ziran
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Emergency Department, Linyi People's Hospital, Linyi, 276003, Shandong, China.
authors.forename: Hongyan
authors.initials: H
authors.lastname: Lei
authors.affiliation: Emergency Department, Linyi People's Hospital, Linyi, 276003, Shandong, China.
authors.forename: Mei
authors.initials: M
authors.lastname: Zheng
authors.affiliation: Emergency Department, Linyi People's Hospital, Linyi, 276003, Shandong, China.
authors.forename: Yuxin
authors.initials: Y
authors.lastname: Li
authors.affiliation: Emergency Department, Linyi People's Hospital, Linyi, 276003, Shandong, China.
authors.forename: Yansen
authors.initials: Y
authors.lastname: Cui
authors.affiliation: Department of Neurology, Liaocheng People's Hospital, No.67 Dongchangxi Road, Liaocheng, 252000, Shandong, China. haofanglph@yeah.net.
authors.forename: Fang
authors.initials: F
authors.lastname: Hao
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics*; D000483:Alleles; D000544:Alzheimer Disease / Q000235:genetics*; D005006:Ethnicity / Q000235:genetics; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D026502:LDL-Receptor Related Proteins / Q000235:genetics*; D026901:Membrane Transport Proteins / Q000235:genetics*; D008957:Models, Genetic; D034041:Monomeric Clathrin Assembly Proteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D017594:Publication Bias
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C490895:GAB2 protein, human; D026502:LDL-Receptor Related Proteins; D026901:Membrane Transport Proteins; D034041:Monomeric Clathrin Assembly Proteins; C439003:PICALM protein, human; C102582:SORL1 protein, human
keywords: Alzheimer’s disease; GAB2; PICALM; SORL1; Single nucleotide polymorphisms