KIAA1462, a coronary artery disease associated gene, is a candidate gene for late onset Alzheimer disease in APOE carriers

PLoS One. 2013 Dec 12;8(12):e82194. doi: 10.1371/journal.pone.0082194. eCollection 2013.

Abstract

Alzheimer disease (AD) is a devastating neurodegenerative disease affecting more than five million Americans. In this study, we have used updated genetic linkage data from chromosome 10 in combination with expression data from serial analysis of gene expression to choose a new set of thirteen candidate genes for genetic analysis in late onset Alzheimer disease (LOAD). Results in this study identify the KIAA1462 locus as a candidate locus for LOAD in APOE4 carriers. Two genes exist at this locus, KIAA1462, a gene associated with coronary artery disease, and "rokimi", encoding an untranslated spliced RNA The genetic architecture at this locus suggests that the gene product important in this association is either "rokimi", or a different isoform of KIAA1462 than the isoform that is important in cardiovascular disease. Expression data suggests that isoform f of KIAA1462 is a more attractive candidate for association with LOAD in APOE4 carriers than "rokimi" which had no detectable expression in brain.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles
  • Alzheimer Disease / genetics*
  • Apolipoprotein E4 / genetics*
  • Brain / metabolism
  • Brain / pathology
  • Cell Adhesion Molecules / genetics*
  • Chromosomes, Human, Pair 10 / genetics
  • Coronary Artery Disease / genetics*
  • Databases, Genetic
  • Exons / genetics
  • Female
  • Gene Expression Regulation
  • Genetic Association Studies*
  • Genetic Loci
  • Genetic Predisposition to Disease*
  • Genome, Human / genetics
  • Heterozygote
  • Humans
  • Introns / genetics
  • Linkage Disequilibrium / genetics
  • Lod Score
  • Male
  • Polymorphism, Single Nucleotide / genetics
  • RNA / isolation & purification
  • Real-Time Polymerase Chain Reaction

Substances

  • Apolipoprotein E4
  • Cell Adhesion Molecules
  • JCAD protein, human
  • RNA