title: Is alpha-T catenin (VR22) an Alzheimer's disease risk gene?
abstract: BACKGROUND
  Recently, conflicting reports have been published on the potential role of genetic variants in the alpha-T catenin gene (VR22; CTNNA3) on the risk for Alzheimer's disease. In these papers, evidence for association is mostly observed in multiplex families with Alzheimer's disease, whereas case-control samples of sporadic Alzheimer's disease are predominantly negative.
  
  
  METHODS
  After sequencing VR22 in multiplex families with Alzheimer's disease linked to chromosome 10q21, we identified a novel non-synonymous (Ser596Asn; rs4548513) single nucleotide polymorphism (SNP). This and four non-coding SNPs were assessed in two independent samples of families with Alzheimer's disease, one with 1439 subjects from 437 multiplex families with Alzheimer's disease and the other with 489 subjects from 217 discordant sibships.
  
  
  RESULTS
  A weak association with the Ser596Asn SNP in the multiplex sample, predominantly in families with late-onset Alzheimer's disease (p = 0.02), was observed. However, this association does not seem to contribute substantially to the chromosome 10 Alzheimer's disease linkage signal that we and others have reported previously. No evidence was found of association with any of the four additional SNPs tested in the multiplex families with Alzheimer's disease. Finally, the Ser596Asn change was not associated with the risk for Alzheimer's disease in the independent discordant sibship sample.
  
  
  CONCLUSIONS
  This is the first study to report evidence of an association between a potentially functional, non-synonymous SNP in VR22 and the risk for Alzheimer's disease. As the underlying effects are probably small, and are only seen in families with multiple affected members, the population-wide significance of this finding remains to be determined.
authors.forename: Lars
authors.initials: L
authors.lastname: Bertram
authors.forename: Kristina
authors.initials: K
authors.lastname: Mullin
authors.forename: Michele
authors.initials: M
authors.lastname: Parkinson
authors.forename: Monica
authors.initials: M
authors.lastname: Hsiao
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Moscarillo
authors.forename: Steven L
authors.initials: SL
authors.lastname: Wagner
authors.forename: K David
authors.initials: KD
authors.lastname: Becker
authors.forename: Gonul
authors.initials: G
authors.lastname: Velicelebi
authors.forename: Deborah
authors.initials: D
authors.lastname: Blacker
authors.forename: Rudolph E
authors.initials: RE
authors.lastname: Tanzi
mesh_terms: D000544:Alzheimer Disease / Q000235:genetics*; D019943:Amino Acid Substitution; D005190:Family; D020022:Genetic Predisposition to Disease; D006801:Humans; D015810:Linkage Disequilibrium; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D051178:alpha Catenin / Q000235:genetics*
chemical_list: D051178:alpha Catenin