Genetic association of the very low density lipoprotein (VLDL) receptor gene with sporadic Alzheimer's disease
- 1 October 1995
- journal article
- research article
- Published by Springer Science and Business Media LLC in Nature Genetics
- Vol. 11 (2), 207-209
- https://doi.org/10.1038/ng1095-207
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). 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.Keywords
This publication has 23 references indexed in Scilit:
- Apolipoprotein E4 allele in a population–based study of early–onset Alzheimer's diseaseNature Genetics, 1994
- ApoE–ε4 and early–onset Alzheimer'sNature Genetics, 1994
- A high frequency of apolipoprotein E4 isoprotein in Japanese patients with late-onset nonfamilial Alzheimer's diseaseNeuroscience Letters, 1993
- Apolipoprotein E in sporadic Alzheimer's disease: Allelic variation and receptor interactionsNeuron, 1993
- Linkage of late-onset Alzheimer's disease with apolipoprotein E type 4 on chromosome 19The Lancet, 1993
- Apolipoprotein E ∈4 allele distributions in late-onset Alzheimer's disease and in other amyloid-forming diseasesThe Lancet, 1993
- Apolipoprotein E polymorphism and Alzheimer's diseaseThe Lancet, 1993
- Gene Dose of Apolipoprotein E Type 4 Allele and the Risk of Alzheimer's Disease in Late Onset FamiliesScience, 1993
- Association of apolipoprotein E allele ϵ4 with late‐onset familial and sporadic Alzheimer's diseaseNeurology, 1993
- Apolipoprotein E: high-avidity binding to beta-amyloid and increased frequency of type 4 allele in late-onset familial Alzheimer disease.Proceedings of the National Academy of Sciences of the United States of America, 1993