title: Apolipoprotein Eepsilon4 modifies Alzheimer's disease onset in an E280A PS1 kindred.
abstract: We previously have identified a large kindred from Colombia in which Alzheimer's disease (AD) is caused by the E280A presenilin 1 (PS1) mutation. The objective of this study was to examine whether environmental and genetic factors are responsible for variation in the phenotypic expression of the E280A PS1 mutation. We genotyped coding and promoter polymorphisms of the APOE gene in carriers of the E280A PS1 mutation. Kaplan-Meier product-limit and Cox proportional hazard models were used in the statistical analyses. DNA was available from 114 carriers of the E280A PS1 mutation, including 52 subjects with AD. APOE epsilon 4 allele carriers were more likely to develop AD at an earlier age than subjects without the epsilon 4 allele (hazard ratio, 2.07; 95% confidence interval, 1.07-3.99; p = 0.030). Subjects with low education were more likely to develop AD later than those with higher education (hazard ratio, 0.476; 95% confidence interval, 0.26-0.87). Low educational level was associated with rural residence (p < 0.001). Promoter APOE variants did not influence either the onset or the duration of the disease. This study is the first to our knowledge to demonstrate that genetic and environmental factors influence age of onset in a kindred with a familial AD mutation.
authors.affiliation: Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, USA.
authors.forename: Pau
authors.initials: P
authors.lastname: Pastor
authors.forename: Catherine M
authors.initials: CM
authors.lastname: Roe
authors.forename: Andrés
authors.initials: A
authors.lastname: Villegas
authors.forename: Gabriel
authors.initials: G
authors.lastname: Bedoya
authors.forename: Sumi
authors.initials: S
authors.lastname: Chakraverty
authors.forename: Gloria
authors.initials: G
authors.lastname: García
authors.forename: Victoria
authors.initials: V
authors.lastname: Tirado
authors.forename: Joanne
authors.initials: J
authors.lastname: Norton
authors.forename: Silvia
authors.initials: S
authors.lastname: Ríos
authors.forename: Maribel
authors.initials: M
authors.lastname: Martínez
authors.forename: Kenneth S
authors.initials: KS
authors.lastname: Kosik
authors.forename: Francisco
authors.initials: F
authors.lastname: Lopera
authors.forename: Alison M
authors.initials: AM
authors.lastname: Goate
mesh_terms: D000328:Adult; D017668:Age of Onset; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D000544:Alzheimer Disease / Q000235:genetics* / Q000473:pathology*; D053327:Apolipoprotein E4; D001057:Apolipoproteins E / Q000235:genetics*; D003105:Colombia; D004247:DNA / Q000235:genetics; D004493:Education; D004777:Environment; D005260:Female; D006579:Heterozygote; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D009154:Mutation / Q000235:genetics / Q000502:physiology; D010375:Pedigree; D010641:Phenotype; D011110:Polymorphism, Genetic / Q000235:genetics; D053764:Presenilin-1; D011401:Promoter Regions, Genetic / Q000235:genetics; D012424:Rural Population; D016019:Survival Analysis
chemical_list: D053327:Apolipoprotein E4; D001057:Apolipoproteins E; D008565:Membrane Proteins; C508853:PSEN1 protein, human; D053764:Presenilin-1; D004247:DNA