Analysis of C9orf72 Intermediate Alleles in a Retrospective Cohort of Neurological Patients: Risk Factors for Alzheimer's Disease?
J Alzheimers Dis
; 81(4): 1445-1451, 2021.
Article
em En
| MEDLINE
| ID: mdl-33935096
ABSTRACT
BACKGROUND:
C9orf72 hexanucleotide GGGGCC (G4C2) large repeat expansions within the first intron of the gene are a major cause of familial frontotemporal dementia, but also of apparently sporadic cases. Alleles withâ>â30 repeats are often considered pathogenic, but the repeat length threshold is still undefined. It is also unclear if C9orf72 intermediate alleles (9-30 repeats) have clinically significant effects.OBJECTIVES:
We correlated the presence of C9orf72 intermediate alleles with clinical diagnoses in a perspective cohort referred to a secondary memory clinic.METHODS:
All samples were genotyped with AmplideXPCR/CE C9ORF72 Kit (Asuragen, Inc), an optimized C9orf72 PCR amplification reagent.RESULTS:
We showed that in patients with Alzheimer's disease (AD) the frequency of the intermediate repeat alleles was significantly increased versus controls (34/54, 63%AD versus 16/39, 41%CTRLs, *pâ=â0.01, OR 2.91 CI 95%1.230-6.077), whereas no significant differences (pâ>â0.05) were observed when comparing all other dementias with non-demented individuals.CONCLUSION:
Our findings suggest that C9orf72 intermediate repeat units may represent a genetic risk factor, contributing to the occurrence of AD. Nevertheless, further longitudinal studies, including larger cohort of subjects with intermediate alleles with long-term follow-up, would be needed to confirm these results.Palavras-chave
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Base de dados:
MEDLINE
Assunto principal:
Predisposição Genética para Doença
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Expansão das Repetições de DNA
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Alelos
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Doença de Alzheimer
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Proteína C9orf72
Tipo de estudo:
Etiology_studies
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Observational_studies
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Risk_factors_studies
Limite:
Aged
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Aged80
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article