An updated meta-analysis of the association between SORL1 variants and the risk for sporadic Alzheimer's disease

J Alzheimers Dis. 2013;37(2):429-37. doi: 10.3233/JAD-130533.

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.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alzheimer Disease / genetics*
  • China
  • Databases, Bibliographic / statistics & numerical data
  • Genetic Predisposition to Disease*
  • Humans
  • LDL-Receptor Related Proteins / genetics*
  • Linkage Disequilibrium
  • Membrane Transport Proteins / genetics*
  • Polymorphism, Single Nucleotide / genetics*

Substances

  • LDL-Receptor Related Proteins
  • Membrane Transport Proteins
  • SORL1 protein, human