title: Apolipoprotein gene E4 allele promoter polymorphisms as risk factors for Alzheimer's disease.
abstract: Alzheimer's disease is a complex neurodegenerative disorder, characterized by progressive cognitive decline and distinct neuropathology. The apolipoprotein gene E4 allele (APOE 4) is a major risk factor for the disease. Promoter polymorphisms at -491 and -427 may also contribute to the risk. We examined the two polymorphisms in 178 Alzheimer's patients and 141 controls. The -491AA genotype was overrepresented among the patients (68 versus 54%, P=0.01). However, in patients who were APOE4 carriers, the -491AA genotype more than doubled the risk [odds ratio (OR)=2.5; 95% confidence interval (CI)=1.2-5.4], especially in combination with -427TT [odds ratio (OR)=3.3; 95% confidence interval (CI)=1.5-7.7]. Moreover, the -491A/-427T/APOE4/APOC1A haplotype was threefold higher for patients. These results contribute to the evidence that regulation of APOE4 expression modulates risk for Alzheimer's disease.
authors.affiliation: Institute of Molecular Medicine and Genetics, Medical College of Georgia, Augusta, Georgia, USA.
authors.forename: Ginny R
authors.initials: GR
authors.lastname: Parker
authors.forename: Heather M
authors.initials: HM
authors.lastname: Cathcart
authors.forename: Rong
authors.initials: R
authors.lastname: Huang
authors.forename: Irene S
authors.initials: IS
authors.lastname: Lanham
authors.forename: Elizabeth H
authors.initials: EH
authors.lastname: Corder
authors.forename: Shirley E
authors.initials: SE
authors.lastname: Poduslo
mesh_terms: D000544:Alzheimer Disease / Q000235:genetics*; D053327:Apolipoprotein E4; D001057:Apolipoproteins E / Q000235:genetics*; D017931:DNA Primers; D005786:Gene Expression Regulation; D006580:Genetic Carrier Screening; D005838:Genotype; D005845:Georgia; D006801:Humans; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D012016:Reference Values; D012307:Risk Factors; D013781:Texas
chemical_list: D053327:Apolipoprotein E4; D001057:Apolipoproteins E; D017931:DNA Primers