title: Polymorphisms in the human apolipoprotein-J/clusterin gene: ethnic variation and distribution in Alzheimer's disease.
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.
authors.affiliation: Gertrude H. Sergievsky Center, Columbia University, New York, NY 10032, USA.
authors.forename: B
authors.initials: B
authors.lastname: Tycko
authors.forename: L
authors.initials: L
authors.lastname: Feng
authors.forename: L
authors.initials: L
authors.lastname: Nguyen
authors.forename: A
authors.initials: A
authors.lastname: Francis
authors.forename: A
authors.initials: A
authors.lastname: Hays
authors.forename: W Y
authors.initials: WY
authors.lastname: Chung
authors.forename: M X
authors.initials: MX
authors.lastname: Tang
authors.forename: Y
authors.initials: Y
authors.lastname: Stern
authors.forename: A
authors.initials: A
authors.lastname: Sahota
authors.forename: H
authors.initials: H
authors.lastname: Hendrie
authors.forename: R
authors.initials: R
authors.lastname: Mayeux
mesh_terms: D001741:Black or African American; D000544:Alzheimer Disease / Q000235:genetics*; D000595:Amino Acid Sequence; D001216:Asparagine; D001483:Base Sequence; D044383:Black People / Q000235:genetics; D051152:Clusterin; D017931:DNA Primers; D004198:Disease Susceptibility; D005006:Ethnicity / Q000235:genetics*; D005091:Exons; D014644:Genetic Variation; D006023:Glycoproteins / Q000235:genetics*; D006031:Glycosylation; D006630:Hispanic or Latino / Q000235:genetics; D006639:Histidine; D006801:Humans; D018832:Molecular Chaperones; D008969:Molecular Sequence Data; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D018807:Polymorphism, Single-Stranded Conformational; D014481:United States; D044465:White People / Q000235:genetics
chemical_list: C495242:CLU protein, human; D051152:Clusterin; D017931:DNA Primers; D006023:Glycoproteins; D018832:Molecular Chaperones; D006639:Histidine; D001216:Asparagine