The APOE ε 2 allele increases the risk of earlier age at onset in Machado-Joseph disease

Conceição Bettencourt, Mafalda Raposo, Nadiya Kazachkova, Teresa Cymbron, Cristina Santos, Teresa Kay, João Vasconcelos, Patrícia Maciel, Karina C. Donis, Maria Luiza Saraiva-Pereira, Laura B. Jardim, Jorge Sequeiros, Manuela Lima

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Objective: To investigate a modulating effect of the apolipoprotein E (APOE) polymorphism on age at onset of Machado-Joseph disease (MJD). Design: 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. Setting: 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)nin 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 å2 allele was associated with an onset before age 39 years (odds ratio, 5.00; 95% CI, 1.18-21.14). Conclusion: The polymorphism at the APOE gene plays a role as a genetic modifier of MJD phenotype. ©2011 American Medical Association. All rights reserved.
Original languageEnglish
Pages (from-to)1580-1583
JournalArchives of Neurology
Issue number12
Publication statusPublished - 1 Dec 2011


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