Polymorphisms in the human apolipoprotein-J/clusterin gene: ethnic variation and distribution in Alzheimer's disease

Hum Genet. 1996 Oct;98(4):430-6. doi: 10.1007/s004390050234.

Abstract

Apolipoprotein-J/clusterin (APOJ/CLI) shares many biological properties with apolipoprotein-E (APOE) including, but not limited to, avid binding with beta-amyloid peptide. Thus, APOJ/CLI warrants scrutiny as a candidate Alzheimer's disease (AD) susceptibility gene. We identified seven nucleotide sequence polymorphisms in APOJ/ CLI, two of which, in exon 7, after the predicted amino acid sequence. The JVIIB variant is an asparagine-to-histidine substitution, which deletes a glycosylation signal at amino acid 317; the JVIIC variant is an aspartate-to-asparagine substitution, which forms a new glycosylation signal at position 328. Both of these coding variants, as well as two neutral polymorphisms in exon 2, were more frequent in African-Americans than Hispanics and were rare in Caucasians. However, no individual coding or noncoding variant was consistently associated with AD. At the population level, APOJ/CLI polymorphisms are frequent among persons of African descent, but probably do not alter susceptibility to AD.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Alzheimer Disease / genetics*
  • Amino Acid Sequence
  • Asparagine
  • Base Sequence
  • Black People / genetics
  • Black or African American
  • Clusterin
  • DNA Primers
  • Disease Susceptibility
  • Ethnicity / genetics*
  • Exons
  • Genetic Variation*
  • Glycoproteins / genetics*
  • Glycosylation
  • Hispanic or Latino / genetics
  • Histidine
  • Humans
  • Molecular Chaperones*
  • Molecular Sequence Data
  • Point Mutation
  • Polymerase Chain Reaction
  • Polymorphism, Genetic*
  • Polymorphism, Single-Stranded Conformational
  • United States
  • White People / genetics

Substances

  • CLU protein, human
  • Clusterin
  • DNA Primers
  • Glycoproteins
  • Molecular Chaperones
  • Histidine
  • Asparagine