title: Genetic association studies between Alzheimer's disease and two polymorphisms in the low density lipoprotein receptor-related protein gene.
abstract: The E*4 allele of apolipoprotein E (APOE) is a major risk factor for Alzheimer's disease (AD) but the underlying mechanism is unknown. The low density lipoprotein receptor-related protein (LRP) is directly involved in APOE metabolism and therefore may alter the risk of AD associated with APOE. Two common polymorphisms, a tetranucleotide repeat in the 5'-region and a same-sense mutation in exon 3, are present in the LRP gene. Three studies have reported conflicting association of the tetranucleotide polymorphism with AD. The only study of the exon 3 polymorphism found a significant association with AD. In this study we examined the association of these two LRP polymorphisms with sporadic late-onset AD. No significant association was observed between the tetranucleotide polymorphism and AD. While the overall genotype and allele frequencies for the LRP exon 3 polymorphism were comparable between AD cases and controls, the frequency of the TT genotype was significantly higher in controls than AD (5.7% vs. 2.5%; P < 0.01). Stratification of the data by APOE genotypes indicated that the protective effect associated with the TT genotype was confined to APOE*4 carriers. Although the effect of the exon 3 polymorphism in our sample is small compared to the previous study, this warrants additional studies to confirm this putative association.
authors.affiliation: Department of Human Genetics, Graduate School of Public Health, Pittsburgh, PA 15261, USA. ikamboh@helix.hgen.pitt.edu
authors.forename: M I
authors.initials: MI
authors.lastname: Kamboh
authors.forename: R E
authors.initials: RE
authors.lastname: Ferrell
authors.forename: S T
authors.initials: ST
authors.lastname: DeKosky
mesh_terms: D017668:Age of Onset; D000368:Aged; D000544:Alzheimer Disease / Q000235:genetics*; D053327:Apolipoprotein E4; D001057:Apolipoproteins E / Q000235:genetics; D005091:Exons; D005260:Female; D005838:Genotype; D006801:Humans; D026503:Low Density Lipoprotein Receptor-Related Protein-1; D008297:Male; D018895:Microsatellite Repeats; D017354:Point Mutation; D011110:Polymorphism, Genetic; D011971:Receptors, Immunologic / Q000235:genetics*; D011973:Receptors, LDL / Q000235:genetics; D012016:Reference Values
chemical_list: D053327:Apolipoprotein E4; D001057:Apolipoproteins E; D026503:Low Density Lipoprotein Receptor-Related Protein-1; D011971:Receptors, Immunologic; D011973:Receptors, LDL