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dc.contributor.authorFrança Júnior, Marcondes Cavalcantept_BR
dc.contributor.authorEmmel, Vanessa Erichsenpt_BR
dc.contributor.authorD'Abreu, Anelyssa Cysne Frotapt_BR
dc.contributor.authorMorelli, Cláudia Vianna Maurerpt_BR
dc.contributor.authorSecolin, Rodrigopt_BR
dc.contributor.authorBonadia, Luciana Cardosopt_BR
dc.contributor.authorSilva, Marilza Santospt_BR
dc.contributor.authorNucci, Anamarlipt_BR
dc.contributor.authorJardim, Laura Bannachpt_BR
dc.contributor.authorPereira, Maria Luiza Saraivapt_BR
dc.contributor.authorMarques Júnior, Wilsonpt_BR
dc.contributor.authorPaulson, Henry L.pt_BR
dc.contributor.authorLopes-Cendes, Iscia Teresinhapt_BR
dc.date.accessioned2018-09-25T02:34:37Zpt_BR
dc.date.issued2012pt_BR
dc.identifier.issn1664-2295pt_BR
dc.identifier.urihttp://hdl.handle.net/10183/182580pt_BR
dc.description.abstractBackground: Age at onset (AO) in Machado–Joseph disease (MJD) is closely associated with the length of the CAG repeat at the mutant ATXN3 allele, but there are other intervening factors. Experimental evidence indicates that the normal ATXN3 allele and the C-terminal heat shock protein 70 (Hsp70)-interacting protein (CHIP) may be genetic modifiers of AO in MJD. Methods:To investigate this hypothesis, we determined the length of normal and expanded CAG repeats at the ATXN3 gene in 210 unrelated patients with MJD. In addition, we genotyped five single nucleotide polymorphisms (SNPs) within the CHIP gene.We first compared the frequencies of the different genotypes in two subgroups of patients who were highly discordant for AO after correction for the length of the expanded CAG allele.The possible modifier effect of each genewas then evaluated in a stepwise multiple linear regression model. Results: AO was associated with the length of the expanded CAG allele (r 2 D0.596, p <0.001). Frequencies of the normal CAG repeats at the ATXN3 gene and of CHIP polymorphisms did not differ significantly between groups with highly discordant ages at onset. However, addition of the normal allele improved the model fit for prediction of AO (r 2 D0.604, p D0.014). Indeed, we found that the normal CAG allele at ATXN3 had a positive independent effect on AO. Conclusion: The normal CAG repeat at the ATXN3 gene has a small but significant influence on AO of MJD.en
dc.format.mimetypeapplication/pdfpt_BR
dc.language.isoengpt_BR
dc.relation.ispartofFrontiers in neurology. Lausanne. Vol. 3 (Nov. 2012), 164, 6 p.pt_BR
dc.rightsOpen Accessen
dc.subjectDoença de Machado-Joseph : Genéticapt_BR
dc.subjectSCA3en
dc.subjectMachado–Joseph diseaseen
dc.subjectPolyQen
dc.subjectModifier genesen
dc.subjectAge at onseten
dc.titleNormal ATXN3 allele but not CHIP polymorphisms modulates age at onset in Machado–Joseph diseasept_BR
dc.typeArtigo de periódicopt_BR
dc.identifier.nrb000875444pt_BR
dc.type.originEstrangeiropt_BR


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