Genetic association of the very low density lipoprotein (VLDL) receptor gene with sporadic Alzheimer's disease.
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.
Okuizumi
K
K
Department of Neurology, Niigata University, Japan.
Onodera
O
O
Namba
Y
Y
Ikeda
K
K
Yamamoto
T
T
Seki
K
K
Ueki
A
A
Nanko
S
S
Tanaka
H
H
Takahashi
H
H
Oyanagi
K
K
Mizusawa
H
H
Kanazawa
I
I
Tsuji
S
S
D000483:Alleles; D000544:Alzheimer Disease / Q000453:epidemiology / Q000235:genetics*; D001057:Apolipoproteins E / Q000235:genetics; D001483:Base Sequence; D002540:Cerebral Cortex / Q000378:metabolism; D002883:Chromosomes, Human, Pair 14; D017931:DNA Primers; D006801:Humans; D007564:Japan; D008969:Molecular Sequence Data; D016017:Odds Ratio; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D011973:Receptors, LDL / Q000235:genetics*; D012016:Reference Values; D012044:Regression Analysis; D012091:Repetitive Sequences, Nucleic Acid; D012307:Risk Factors
D001057:Apolipoproteins E; D017931:DNA Primers; D011973:Receptors, LDL; C036053:VLDL receptor