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Dement Geriatr Cogn Disord. 2008 November; 26(5): 482.
Published online 2008 November 4. doi:  10.1159/000167792
PMCID: PMC2703707

Possible Association between SORL1 and Alzheimer Disease?

Reanalysing the Data of Shibata et al.

Shibata et al. [1] reported that the variants in neuronal sortilin-related receptor (SORL1) were not associated with Alzheimer disease (AD) in a Japanese cohort comprising 180 cases and 130 age-matched controls. The authors performed a genotypic association analysis using 7 single nucleotide polymorphisms (SNPs) that were previously reported to be statistically significant by Rogaeva et al. [2] and subsequently by others [3,4,5]. The authors reported no association with AD. However, they did observe a weak association (p = 0.05) for SNP 8 (rs668387) when restricted to APOE [sm epsilon]4 noncarriers.

We conducted an allelic association analysis of the same data, which shows that 2 SNPs (8 and 24) were significantly associated with AD with p values less than 0.05. Specifically, when all subjects were examined, SNP 24 (rs2282649) and SNP 8 (rs668387) were significant (p < 0.05). However, using a model restricted to elderly APOE [sm epsilon]4 noncarriers, the association became somewhat stronger (SNP 8, p = 0.0163; SNP 24, p = 0.0375). More importantly, the associated variants in the study by Shibata et al. [1] were identical to those in the study by Rogaeva et al. [2]. For SNP 24, the T allele was associated with AD in Caucasians as well as in Japanese people. For SNP 8, the C allele was associated with AD in Caribbean Hispanics, Caucasians, Israeli Arabs, and Japanese people.

In contrast to the original conclusions, this study does support the association between variants in SORL1 and AD in a Japanese population. Although the findings are only marginally significant given the small sample size, this study continues to support the association in both the 3′ and 5′ regions of SORL1.

References

1. Shibata N, Ohnuma T, Baba H, Higashi S, Nishioka K, Arai H. Genetic association between SORL1 polymorphisms and Alzheimer's disease in a Japanese population. Dement Geriatr Cogn Disord. 2008;26:161–164. [PubMed]
2. Rogaeva E, Meng Y, Lee JH, et al. The neuronal sortilin-related receptor SORL1 is genetically associated with Alzheimer disease. Nat Genet. 2007;39:168–177. [PMC free article] [PubMed]
3. Bettens K, Brouwers N, Engelborghs S, De Deyn PP, Van Broeckhoven C, Sleegers K. SORL1 is genetically associated with increased risk for late-onset Alzheimer disease in the Belgian population. Hum Mutat. 2008;29:769–770. [PubMed]
4. Lee JH, Cheng R, Honig LS, Vonsattel JP, Clark L, Mayeux R. Association between genetic variants in SORL1 and autopsy-confirmed Alzheimer disease. Neurology. 2008;70:887–889. [PMC free article] [PubMed]
5. Meng Y, Lee JH, Cheng R, St George-Hyslop P, Mayeux R, Farrer LA. Association between SORL1 and Alzheimer's disease in a genome-wide study. Neuroreport. 2007;18:1761–1764. [PMC free article] [PubMed]

Articles from Dementia and Geriatric Cognitive Disorders are provided here courtesy of Karger Publishers