Genetic association of the very low density lipoprotein (VLDL) receptor gene with sporadic Alzheimer’s disease

Kaoru Okuizumi, Osamu Onodera, Yoshio Namba, Kazuhiko Ikeda, Tokuo Yamamoto, Koji Seki, Akira Ueki, Shinichiro Nanko, Hajime Tanaka, Hitoshi Takahashi, Kiyomitsu Oyanagi, Hidehiro Mizusawa, Ichiro Kanazawa, Shoji Tsuji

Research output: Contribution to journalArticlepeer-review

156 Citations (Scopus)

Abstract

A specific isoform of apolipoprotein E has been associated with the accelerated rate of disease expression of sporadic Alzheimer’s disease (AD) and late-onset familial AD (FAD)1–12. An earlier age at onset has also been demonstrated in familial AD patients with mutations in the amyloid precursor protein (APR) gene (APP717 and APP670/671)13 carrying the APOEɛ-4 allele compared to those who do not, but not in familial AD patients with APP692 or 693 mutations14, or in chromosome 14-linked familial AD patients15.Hypothesizing that receptors for apoE-containing lipoprotein16–22 act as a potential risk factor for AD, we performed an association study using a polymorphic triplet (CGG) repeat21,23 in the gene for the VLDL receptor (VLDL-R), a receptor for apoE-containing lipoproteins.The frequency of the 5-repeat allele was significantly higher in all of the Japanese sporadic AD patients (P<0.02) than in the Japanese controls. Moreover, the odds ratio was significantly increased in the AD patients homozygous for the 5-repeat allele (OR=2.1,95% Cl=[1.1–4.2]). Multiple logistic regression analysis reveals that the relative risk conferred by the presence of two copies of the 5-repeat allele and at least one copy of the APOEɛ-4 allele is 8.7 (95% Cl=[2.9–25.8]). Our results suggest that the VLDL-R gene is a susceptibility gene for AD.

Original languageEnglish
Pages (from-to)207-209
Number of pages3
JournalNature Genetics
Volume11
Issue number2
DOIs
Publication statusPublished - 1995 Oct

ASJC Scopus subject areas

  • Genetics

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