No association between the very low density lipoprotein receptor gene and late-onset Alzheimer's disease nor interaction with the apolipoprotein E gene in population-based and clinic samples.
It is now commonly known that possession of one of the three common alleles of the apolipoprotein E (APOE) gene (allele epsilon 4) confers an increased risk for both familial and sporadic Alzheimer's disease (AD), and that this risk is dose-dependent. Other genes that may play a role in AD, either through independent association with the disease or through modification of the existing APOE risk, are under investigation. One such gene, the very low density lipoprotein receptor (VLDL-R) gene, was reported by Okuizumi et al. to be independently associated with AD in a Japanese population, but not interactive with the APOE4 conferred risk. Their clinic-based data set demonstrated a 2-fold increased risk conferred by the 5-repeat allele of a polymorphism in VLDL-R. As recruitment from a clinic rather than a population-based sample may result in a distortion of allele frequencies, as has been shown with APOE allele frequencies, it is important to investigate this association in a population-based study. We have genotyped both population and clinic-based AD data sets at this VLDL-R polymorphism, and we find no independent association between the VLDL-R gene and the occurrence of AD in either sample. Further, despite the biochemical relationship between the VLDL-R and APOE proteins, we find no significant statistical interaction between the alleles at these loci.
Fallin
D
D
Department of Behavioral Medicine, University of South Florida, Tampa 33613, USA.
Gauntlett
A C
AC
Scibelli
P
P
Cai
X
X
Duara
R
R
Gold
M
M
Crawford
F
F
Mullan
M
M
D017668:Age of Onset; D000368:Aged; D000544:Alzheimer Disease / Q000453:epidemiology / Q000235:genetics*; D053327:Apolipoprotein E4; D001057:Apolipoproteins E / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011973:Receptors, LDL / Q000235:genetics*; D012307:Risk Factors
D053327:Apolipoprotein E4; D001057:Apolipoproteins E; D011973:Receptors, LDL; C036053:VLDL receptor