title: The role of apolipoprotein E as a risk factor for an earlier age at onset for Machado-Joseph disease is doubtful.
abstract: Machado-Joseph disease (MJD) is an inherited neurodegenerative disease caused by an expanded CAG repeat in the ATXN3 gene. Although the principal genetic determinant of the age at onset (AAO) is the length of the expanded CAG repeat, the additional genetic contribution of MJD toward the AAO has mostly not yet been clarified. It was recently suggested in two independent studies that apolipoprotein E (APOE) might be associated with AAO variability in MJD patients. To identify the potential modifier effect of APOE polymorphisms on the AAO of MJD patients, 403 patients with MJD (confirmed by molecular tests) from eastern and southeastern China were enrolled in the present study. CAG repeats in the ATXN3 and APOE polymorphisms were genotyped. Data were analyzed using a statistical package. No contribution of APOE polymorphisms to the variance in disease onset was observed using ANCOVA (F = 0.183, P = 0.947). However, significant effects on the AAO of MJD were found for the normal ATXN3 allele and for the interaction of mutant and normal ATXN3 alleles in a multiple linear regression model (P = 0.043 and P = 0.035, respectively). Our study does not support a role for APOE as a genetic modifier of the AAO of MJD. Additionally, our study presents evidence that the normal ATXN3 allele and its interaction with mutant alleles contribute toward AAO variance in MJD patients.
authors.affiliation: Department of Neurology and Institute of Neurology, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China; Department of Neurology and Institute of Neurology, First Affiliated Hospital, Fujian Medical University, Fuzhou, Fujian, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Zhou
authors.affiliation: Department of Neurology and Institute of Neurology, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China; Department of Neurology and Institute of Neurology, First Affiliated Hospital, Fujian Medical University, Fuzhou, Fujian, China.
authors.forename: Wang
authors.initials: W
authors.lastname: Ni
authors.affiliation: Department of Neurology and Institute of Neurology, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Dong
authors.affiliation: Department of Neurology and Institute of Neurology, First Affiliated Hospital, Fujian Medical University, Fuzhou, Fujian, China.
authors.forename: Ning
authors.initials: N
authors.lastname: Wang
authors.affiliation: Department of Neurology and Institute of Neurology, First Affiliated Hospital, Fujian Medical University, Fuzhou, Fujian, China.
authors.forename: Shi-Rui
authors.initials: SR
authors.lastname: Gan
authors.affiliation: Department of Neurology and Institute of Neurology, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China; Department of Neurology and Institute of Neurology, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China.
authors.forename: Zhi-Ying
authors.initials: ZY
authors.lastname: Wu
mesh_terms: D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D000368:Aged; D000483:Alleles; D000704:Analysis of Variance; D001057:Apolipoproteins E / Q000235:genetics* / Q000378:metabolism; D000067699:Ataxin-3; D002648:Child; D015331:Cohort Studies; D005260:Female; D005838:Genotype; D006801:Humans; D016014:Linear Models; D017827:Machado-Joseph Disease / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D020641:Polymorphism, Single Nucleotide; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D012307:Risk Factors; D018911:Trinucleotide Repeats; D055815:Young Adult
chemical_list: D001057:Apolipoproteins E; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D012097:Repressor Proteins; C092341:ATXN3 protein, human; D000067699:Ataxin-3