Department of Geriatrics, Wuxi Mental Health Center, Wuxi, Jiangsu, China.
J Alzheimers Dis. 2013;37(2):429-37. doi: 10.3233/JAD-130533.
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.
阿尔茨海默病（AD）的发病机制尚不清楚；然而，遗传变异在 AD 的发病机制中起着关键作用。据报道，sortilin 相关受体 A 型重复（SORL1，也称为 LR11 或 sorLA）的单核苷酸多态性（SNP）与高加索人群的迟发性 AD 相关。随后，其他研究人员试图在不同的种族人群中验证这一发现。然而，这些发现既有阴性结果，也有阳性结果。为了更准确地评估 SORL1 变体是否与散发性 AD（SAD）相关，我们进行了本文呈现的荟萃分析。检索了包括 PubMed、AlzGene、中国国家知识基础设施（CNKI）和万方在内的数据库，以寻找相关研究。使用优势比（OR）和 95%置信区间（CI）来评估关联研究的强度。共纳入 23 项病例对照研究，涉及 11837 例病例和 20022 例对照。在之前研究中强调的十一个候选 SNP 中，四个 SNP（SNP4、SNP5、SNP8 和 SNP10）使用广义优势比（ORG，无模型方法）和连锁不平衡结构分析与 SAD 显著相关。同时，在当前的荟萃分析中，没有观察到相关 SNP 在高加索人群和亚洲人群之间存在显著的异质性。此外，我们进一步证实，SNP8-SNP9-SNP10 处的 SORL1 三标记单体型 C-G-C 与 SAD 显著相关（OR=1.37，95%CI=1.12-1.66，padj=0.008）。当前的荟萃分析进一步支持了先前的发现，即 SORL1 基因可能与 SAD 风险相关。
