Repeat length variations in ATXN1 and AR modify disease expression in Alzheimer's disease
| العنوان: | Repeat length variations in ATXN1 and AR modify disease expression in Alzheimer's disease |
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| المؤلفون: | Yolande A.L. Pijnenburg, Philip Scheltens, Wiesje M. van der Flier, Iris E. Jansen, Martine J. van Belzen, Merel W. Boogaard, Jacobijn Gussekloo, Stella Trompet, Raymund A.C. Roos, Yvonne J.M. Campman, N. Ahmad Aziz, Aster V.E. Harder, Sarah L. Gardiner |
| المساهمون: | Neurology, Amsterdam Neuroscience - Neurodegeneration, Divisions, APH - Personalized Medicine, APH - Methodology |
| المصدر: | Neurobiology of Aging, 73, 230.e9-230.e17. Elsevier Inc. Neurobiology of aging 73, 230.e9-230.e17 (2019). doi:10.1016/j.neurobiolaging.2018.09.007 Neurobiology of Aging, 73 Gardiner, S L, Harder, A V E, Campman, Y J M, Trompet, S, Gussekloo, J, van Belzen, M J, Boogaard, M W, Roos, R A C, Jansen, I E, Pijnenburg, Y A L, Scheltens, P, van der Flier, W M & Aziz, N A 2019, ' Repeat length variations in ATXN1 and AR modify disease expression in Alzheimer's disease ', Neurobiology of Aging, vol. 73, pp. 230.e9-230.e17 . https://doi.org/10.1016/j.neurobiolaging.2018.09.007 |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | Male, 0301 basic medicine, Oncology, CAG repeat polymorphisms, Aging, genetics [Alzheimer Disease], Disease, Pathogenesis, pathology [Alzheimer Disease], 0302 clinical medicine, genetics [Ataxin-1], Missing heritability problem, AR protein, human, Prospective cohort study, Ataxin-1, Aged, 80 and over, General Neuroscience, Middle Aged, Alzheimer's disease, Huntington disease, Temporal Lobe, genetics [Genetic Variation], 3. Good health, Receptors, Androgen, Cohort, Female, Adult, medicine.medical_specialty, Guanine, genetics [Polymorphism, Genetic], genetics [Receptors, Androgen], Cytosine, 03 medical and health sciences, Polyglutamine diseases, Atrophy, Alzheimer Disease, Internal medicine, medicine, Humans, Dementia, ATXN1 protein, human, ddc:610, Allele, Aged, Repetitive Sequences, Nucleic Acid, Polymorphism, Genetic, business.industry, Adenine, Genetic Variation, pathology [Temporal Lobe], medicine.disease, Missing heritability, 030104 developmental biology, Neurology (clinical), Geriatrics and Gerontology, business, 030217 neurology & neurosurgery, Genome-Wide Association Study, Developmental Biology |
| الوصف: | Genomewide association studies (GWASs) have contributed greatly to unraveling the genetic basis of Alzheimer's disease (AD). However, a large amount of “missing heritability” remains. In this exploratory study, we investigated the effect of cytosine-adenine-guanine (CAG) repeats in polyglutamine disease–associated genes (PDAGs) on the risk of AD and its expression. In a cohort of 959 patients diagnosed with AD (Amsterdam Dementia cohort) and 4106 cognitively healthy participants (Leiden 85-plus Study and the Prospective Study of Pravastatin in the Elderly at Risk), we determined the CAG repeat sequences in ATXN1, ATXN2, ATXN3, CACNA1A, ATXN7, TBP, HTT, ATN1, and AR. We did not find a significant association between the risk of AD and variations in CAG repeat numbers of PDAGs. However, we found that differences in CAG repeat numbers in ATXN1, ATXN2, and AR were significantly associated with several clinical and imaging features in AD patients. Specifically, the association between memory performance in patients with AD and the CAG repeat size in the longer ATXN1 allele, and the association between atrophy in the medial temporal lobes and the CAG repeat number in the longer AR allele remained significant after correction for multiple testing. Our findings suggest that repeat polymorphisms in ATXN1 and AR can act as important genetic modifiers of AD, warranting further scrutiny of their role in its missing heritability and pathogenesis. |
| اللغة: | English |
| تدمد: | 0197-4580 |
| DOI: | 10.1016/j.neurobiolaging.2018.09.007 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::6a44af72365ba7bf897e11cefc146843 https://hdl.handle.net/1887/116663 |
| Rights: | CLOSED |
| رقم الانضمام: | edsair.doi.dedup.....6a44af72365ba7bf897e11cefc146843 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 01974580 |
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| DOI: | 10.1016/j.neurobiolaging.2018.09.007 |