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)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).
Conclusion The polymorphism at the APOE gene plays a role as a genetic modifier of MJD phenotype.