Normal ATXN3 allele but not CHIP polymorphisms modulates age at onset in Machado-Joseph Disease
| Autor: | Wilson Marques, Henry L. Paulson, Rodrigo Secolin, Anelyssa D'Abreu, Maria Luiza Saraiva-Pereira, Vanessa Erichsen Emmel, Laura Bannach Jardim, Luciana Cardoso Bonadia, Marcondes C. França, Marilza Santos da Silva, Cláudia Vianna Maurer-Morelli, Anamarli Nucci, Iscia Lopes-Cendes |
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| Jazyk: | angličtina |
| Rok vydání: | 2012 |
| Předmět: |
congenital
hereditary and neonatal diseases and abnormalities Mutant Single-nucleotide polymorphism Multiple linear regression model Biology lcsh:RC346-429 SCA3 modifier genes Genotype medicine Genética [Doença de Machado-Joseph] Allele Gene lcsh:Neurology. Diseases of the nervous system Original Research Genetics Age at onset Machado-Joseph Disease medicine.disease Hsp70 Modifier genes Neurology PolyQ Neurology (clinical) Machado–Joseph disease age at onset Neuroscience |
| Zdroj: | Frontiers in Neurology, Vol 3 (2012) Repositório Institucional da UFRGS Universidade Federal do Rio Grande do Sul (UFRGS) instacron:UFRGS Frontiers in Neurology |
| ISSN: | 1664-2295 |
| Popis: | Background: 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 gene was then evaluated in a stepwise multiple linear regression model. Results: AO was associated with the length of the expanded CAG allele (r2 = 0.596, p |
| Databáze: | OpenAIRE |
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