title: The APOE ε2 allele increases the risk of earlier age at onset in Machado-Joseph disease.
abstract: OBJECTIVE
  To investigate a modulating effect of the apolipoprotein E (APOE) polymorphism on age at onset of Machado-Joseph disease (MJD).
  
  
  METHODS
  We collected blood samples from 192 patients with MJD and typed the APOE polymorphism. Patients The 192 patients with MJD included 59 from the Azores, 73 from mainland Portugal, and 60 from Brazil.
  
  
  METHODS
  Academic research center.
  
  
  RESULTS
  Cases with the ε2/ε3 genotype had an earlier onset compared with those with the ε3/ε3 or the ε3/ε4 genotype. In this series of patients, the presence of an APOE ε2 allele implies a decrease of nearly 5 years in the age at onset. When combining several other predictors in a general linear model, namely, the presence/absence of the APOE ε2 allele, with the size of the (CAG)(n) in expanded alleles, the model was significantly improved and the explanation of onset variance was raised from 59.8% to 66.5%. Furthermore, the presence of the ε2 allele was associated with an onset before age 39 years (odds ratio, 5.00; 95% CI, 1.18-21.14).
  
  
  CONCLUSIONS
  The polymorphism at the APOE gene plays a role as a genetic modifier of MJD phenotype.
authors.affiliation: Center of Research in Natural Resources and Department of Biology, University of Azores, Rua Mãe de Deus-Apartado 1422, 9501-801 Ponta Delgada, Azores, Portugal. mcbettencourt@uac.pt
authors.forename: Conceição
authors.initials: C
authors.lastname: Bettencourt
authors.forename: Mafalda
authors.initials: M
authors.lastname: Raposo
authors.forename: Nadiya
authors.initials: N
authors.lastname: Kazachkova
authors.forename: Teresa
authors.initials: T
authors.lastname: Cymbron
authors.forename: Cristina
authors.initials: C
authors.lastname: Santos
authors.forename: Teresa
authors.initials: T
authors.lastname: Kay
authors.forename: João
authors.initials: J
authors.lastname: Vasconcelos
authors.forename: Patrícia
authors.initials: P
authors.lastname: Maciel
authors.forename: Karina C
authors.initials: KC
authors.lastname: Donis
authors.forename: Maria Luiza
authors.initials: ML
authors.lastname: Saraiva-Pereira
authors.forename: Laura B
authors.initials: LB
authors.lastname: Jardim
authors.forename: Jorge
authors.initials: J
authors.lastname: Sequeiros
authors.forename: Manuela
authors.initials: M
authors.lastname: Lima
mesh_terms: D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D000368:Aged; D000483:Alleles; D053329:Apolipoprotein E2 / Q000235:genetics*; D002648:Child; D042241:Early Diagnosis; D005260:Female; D005838:Genotype; D006801:Humans; D017827:Machado-Joseph Disease / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D011110:Polymorphism, Genetic; D012306:Risk; D055815:Young Adult
chemical_list: D053329:Apolipoprotein E2