Affiliations: [a] Department of Geriatrics, Wuxi Mental Health Center, Wuxi, Jiangsu, China | [b] Department of Clinical Psychology, Wuxi Mental Health Center, Wuxi, Jiangsu, China | [c] Brain Science Basic Laboratory, Wuxi Mental Health Center, Wuxi, Jiangsu, China
Correspondence:
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Correspondence to: Chunhui Jin, Wuxi Mental Health Center, Wuxi 214151, China. Tel.: +86 510 83250132; Fax: +86 510 83012201; E-mail: jch1029@126.com; Zaohuo Cheng, Wuxi Mental Health Center, Wuxi 214151, China. Tel.: +86 510 83030359; Fax: +86 510 83012201; E-mail: chengzaohuo@126.com.
Abstract: The pathogenetic mechanism of Alzheimer's disease (AD) is still unknown; however, genetic variants play a critical role in the pathogenesis of AD. It has been reported that single nucleotide polymorphisms (SNPs) of the sortilin-related receptor with A-type repeats (SORL1, also called LR11 or sorLA) are associated with late-onset AD in Caucasian populations. Subsequently, other researchers have attempted to validate this finding in different ethnic populations. However, these findings have produced both negative and positive results. To derive a more precise estimation of whether SORL1 variants are associated with sporadic AD (SAD), we performed the meta-analysis presented in this manuscript. Databases including PubMed, AlzGene, the China National Knowledge Infrastructure (CNKI), and Wan Fang were searched to find relevant studies. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of the association studies. A total of twenty-three case-control studies involving 11,837 cases and 20,022 controls were included. Among the eleven candidate SNPs highlighted in the previous study, four SNPs (SNP 4, SNP 5, SNP 8 and SNP 10) showed a significant association with SAD using a generalized odds ratio (ORG, a model-free approach) and linkage disequilibrium structure analysis. Meanwhile, no significant heterogeneity between the Caucasian and Asian populations for the associated SNPs was observed in the current meta-analysis. Moreover, we further confirmed that the SORL1 three-marker haplotype C-G-C at SNP 8-SNP 9-SNP 10 was significantly associated with SAD (OR = 1.37, 95% CI = 1.12–1.66, padj = 0.008). The current meta-analysis further supports the previous findings that the SORL1 gene may be associated with SAD risk.
Keywords: Allele, Alzheimer's disease, association, single nucleotide polymorphism, SORL1
