Genetic association between clusterin polymorphisms and Alzheimer's disease in a Japanese population

Background: Previous papers have reported that clusterin (CLU, also called apolipoprotein J) maintains amyloid β-peptide (Aβ) solubility and protects against Aβ neurotoxicity. Recently, two large genome-wide association studies (GWAS) identified that a specific single nucleotide polymorphism (SNP) on the gene has been reported to modify the risk for Alzheimer's disease (AD). The present study aimed to investigate whether common single nucleotide polymorphisms (SNP) of the CLU gene are associated with AD.

Methods: Six SNP, genotyped using TaqMan technology, were analyzed using a case-control study design. Furthermore, an analysis of the cases divided according to apolipoprotein E (APO E) status was also carried out. Our case-control dataset consisted of 180 AD patients and 130 age-matched controls.

Results: The present study failed to detect any association between the SNP of the CLU gene and AD. Although rs7982 and rs1532277 showed marginal association in the APO E4 negative group, the linkage disequilibrium analysis results suggest this to be a false positive.

Conclusion: The negative associations were mainly the result of our small sample size. Larger genetic studies in different ethnics and future meta-analysis are needed to clarify the relationship between the CLU gene and AD.