Genetic variation in APOE, GRN, and TP53 are phenotype modifiers in frontotemporal dementia
| Autor: | Eliecer Coto, Pau Pastor, Maria Serpente, Sandro Sorbi, Benedetta Nacmias, Victoria Alvarez, Raffaele Maletta, Livia Bernardi, Sergio Pérez-Oliveira, Paola Caroppo, Roberta Ghidoni, Manuel Menéndez-González, Irene Piaceri, Raffaele Ferrari, Beatriz De la Casa-Fages, Daniela Galimberti, Raquel Sánchez-Valle, Monica Diez-Fairen, Oriol Dols-Icardo, Ignacio Illán-Gala, Ifgc, Daniel Queimaliños-Perez, Elio Scarpini, Julie van der Zee, Amalia C. Bruni, Christine Van Broeckhoven, Maria Rosário Almeida, Giacomina Rossi, Irene Rosas, Carmen Martínez, Silvia Bagnoli, Francisco Grandas, Barbara Borroni, Jordi Clarimón, Alberto Lleó, Giuliano Binetti, Luisa Benussi, Anna Antonell, Maria Anfossi |
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| Přispěvatelé: | EU EOD Consortium |
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Apolipoprotein E Male Aging Heterozygote Biology 03 medical and health sciences 0302 clinical medicine Apolipoproteins E Progranulins C9orf72 mental disorders Genetic variation medicine Humans TP53 Gene Genetic Association Studies Genetics Heterogeneous group C9orf72 Protein Age at onset APOE Frontotemporal dementia GRN Survival probability General Neuroscience Genetic Variation medicine.disease Phenotype 030104 developmental biology Disease risk Female Human medicine Neurology (clinical) Geriatrics and Gerontology Tumor Suppressor Protein p53 030217 neurology & neurosurgery Developmental Biology |
| Zdroj: | Neurobiology of aging |
| ISSN: | 0197-4580 |
| Popis: | Frontotemporal dementia (FTD) is a clinical, genetic, and pathologic heterogeneous group of neurodegenerative diseases. In this study, we investigated the role of APOƐ4, rs5848 in GRN, and rs1042522 in TP53 gene as disease risk factors and/or phenotype modifiers in 440 FTD patients, including 175 C9orf72 expansion carriers. We found that the C9orf72 expansion carriers showing an earlier age at onset (p < 0.001). Among the clinical groups, the FTD-MND (motoneuron disease) showed the lowest survival (hazard ratio [HR] = 4.12), and the progressive nonfluent aphasia group showed the highest onset age (p = 0.03). In our cohort, the rs1042522 in TP53 was associated with disease onset (p = 0.02) and survival (HR = 1.73) and rs5848 GRN with a significantly shorter survival in CC homozygous patients (HR = 1.98). The frequency of APOƐ4 carriers was significantly increased in the C9orf72 noncarriers (p = 0.022). Although validation of our findings is necessary, our results suggest that TP53, GRN, and APOE genes may act as phenotype modifiers in FTD and should be considered in future clinical trials. |
| Databáze: | OpenAIRE |
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