CLU rs9331888 Polymorphism Contributes to Alzheimer's Disease Susceptibility in Caucasian But Not East Asian Populations

Mol Neurobiol. 2016 Apr;53(3):1446-1451. doi: 10.1007/s12035-015-9098-1. Epub 2015 Jan 30.

Abstract

Large-scale genome-wide association studies (GWAS) identified three single nucleotide polymorphisms rs11136000, rs2279590, and rs9331888 in CLU gene to be significantly associated with Alzheimer's disease (AD) in Caucasian ancestry. Both rs11136000 and rs2279590 variants were successfully replicated in Asian population. However, previous studies reported either a weak association or no association between rs9331888 polymorphism and AD in Asian population. Here, we searched the PubMed, AlzGene, and Google Scholar databases. We selected 12 independent studies that evaluated the association between the rs9331888 polymorphism and AD using a case-control design. Using an additive model, we did not identify significant heterogeneity among these 12 studies. We observed significant association between rs9331888 polymorphism and AD in pooled populations (P = 2.26E - 07, odds ratio (OR) = 1.10, 95% confidence interval (CI) 1.06-1.14). In subgroup analysis, we did not identify significant heterogeneity in both Asian and Caucasian populations. We identified significant association in Caucasian population (P = 1.67E - 08, OR = 1.13, 95% CI 1.08-1.18) but not in East Asian population (P = 0.49, OR = 1.02, 95% CI 0.96-1.10).

Keywords: Alzheimer’s disease; Genome-wide association studies (GWAS); Single nucleotide polymorphisms.

Publication types

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

MeSH terms

  • Alleles
  • Alzheimer Disease / ethnology
  • Alzheimer Disease / genetics*
  • Asian People / genetics*
  • Case-Control Studies
  • Clusterin / genetics*
  • Gene Frequency
  • Genetic Predisposition to Disease
  • Humans
  • Odds Ratio
  • Polymorphism, Single Nucleotide*
  • White People / genetics*

Substances

  • CLU protein, human
  • Clusterin