PICALM Gene rs3851179 Polymorphism Contributes to Alzheimer’s Disease in an Asian Population

Abstract

PICALM gene rs3851179 polymorphism was reported to an Alzheimer's disease (AD) susceptibility locus in a Caucasian population. However, recent studies reported consistent and inconsistent results in an Asian population. Four studies indicated no association between rs3851179 and AD in a Chinese population and one study reported weak association in a Japanese population. We consider that the failure to replicate the significant association between rs3851179 and AD may be caused by at least two reasons. The first reason may be the genetic heterogeneity in AD among different populations, and the second may be the relatively small sample size compared with large-scale GWAS in Caucasian ancestry. In order to confirm this view, in this research, we first evaluated the genetic heterogeneity of rs3851179 polymorphism in Caucasian and Asian populations. We then investigated rs3851179 polymorphism in an Asian population by a pooled analysis method and a meta-analysis method. We did not observe significant genetic heterogeneity of rs3851179 in the Caucasian and Asian populations. Our results indicate that rs3851179 polymorphism is significantly associated with AD in the Asian population by both pooled analysis and meta-analysis methods. We believe that our findings will be very useful for future genetic studies in AD.

The Role of PICALM in Alzheimer’s Disease

“…Among others, Chen reported that the association between LOAD and rs3851179 can only be observed in APOE epsilon4 (−) subgroup [48], which is against the proposition that APOE4 and PICALM (rs3851179) synergistically confer risk to AD [49,50]. On the other hand, Liu attributed these replication failures to two basic reasons: (1) the genetic heterogeneity among different populations [51] and (2) the limited sample size compared with that in Caucasian descent [52]. Consistent with which Liu observed no obvious genetic heterogeneity of rs3851179 polymorphism between Fig.…”

PICALM rs3851179 Variant and Alzheimer’s Disease in Asian Population

“…In summary, we think that these three issues are important, and may provide supplementary information about our previous article (Liu et al 2013). …”

“…We thank Wang and colleagues for their interest in our article published in NeuroMolecular Medicine (Liu et al 2013). In this article above, we evaluated the potential association of rs3851179 variant with Alzheimer's disease (AD) in Asian population by a pooled analysis and a metaanalysis.…”

“…We searched the PubMed database to select all the possible studies in the original article (Liu et al 2013). We accept this suggestion and will use multiple literature databases in further studies, including PubMed, AlzGene, Google Scholar and China Knowledge Resource Integrated Database (CNKI), as did in our recent studies (Liu et al 2014;Shen et al 2015;Li et al 2015;Zhang et al 2015).…”

“…We also accept the suggestion about the Cochran's Q test significance level 0.1. In further, we will give an erratum to this article published in NeuroMolecular Medicine (Liu et al 2013).…”