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

Authors: Okuizumi, K  Onodera, O  Namba, Y  Ikeda, K  Yamamoto, T  Seki, K  Ueki, A  Nanko, S  Tanaka, H  Takahashi, H  Oyanagi, K  Mizusawa, H  Kanazawa, I  Tsuji, S 
Citation: Okuizumi K, etal., Nat Genet 1995 Oct;11(2):207-9.
Pubmed: (View Article at PubMed) PMID:7550352
DOI: Full-text: DOI:10.1038/ng1095-207

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). An earlier age at onset has also been demonstrated in familial AD patients with mutations in the amyloid precursor protein (APP) gene (APP717 and APP670/671)13 carrying the APOE epsilon-4 allele compared to those who do not, but not in familial AD patients with APP692 or 693 mutations, or in chromosome 14-linked familial AD patients. Hypothesizing that receptors for apoE-containing lipoproteins act as a potential risk factor for AD, we performed an association study using a polymorphic triplet (CGG) repeat 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% CI = [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 APOE epsilon-4 allele is 8.7 (95% CI = [2.9-25.8]). Our results suggest that the VLDL-R gene is a susceptibility gene for AD.

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CRRD ID: 737739
Created: 2004-02-26
Species: All species
Last Modified: 2004-02-26
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