LRRK2 variation and dementia with Lewy bodies
| Autor: | Neill R. Graff-Radford, Owen A. Ross, David S. Knopman, Val J. Lowe, David T.W. Jones, Melissa E. Murray, Alexandra I. Soto-Ortolaza, Zbigniew K. Wszolek, Ronald C. Petersen, Rosa Rademakers, Joseph E. Parisi, Glenn E. Smith, Monica Sanchez Contreras, Clifford R. Jack, Catherine Labbé, Bradley F. Boeve, Jay A. van Gerpen, Ronald L. Walton, Tanis J. Ferman, Jonathan Graff-Radford, Oswaldo Lorenzo-Betancor, Rodolfo Savica, Nilufer Ertekin-Taner, Kejal Kantarci, Nancy N. Diehl, Michael G. Heckman, Ryan J. Uitti, Dennis W. Dickson, Otto Pedraza |
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| Rok vydání: | 2016 |
| Předmět: |
Lewy Body Disease
Male 0301 basic medicine Parkinson's disease Disease Leucine-Rich Repeat Serine-Threonine Protein Kinase-2 Bioinformatics behavioral disciplines and activities Article 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine mental disorders medicine Humans Dementia Pathological Genetic Association Studies Aged Retrospective Studies Aged 80 and over Alpha-synuclein business.industry Dementia with Lewy bodies Haplotype Brain Middle Aged medicine.disease LRRK2 nervous system diseases Logistic Models 030104 developmental biology Neurology chemistry Mutation alpha-Synuclein Female Human medicine Neurology (clinical) Geriatrics and Gerontology business 030217 neurology & neurosurgery |
| Zdroj: | Parkinsonism and related disorders |
| ISSN: | 1353-8020 |
| DOI: | 10.1016/j.parkreldis.2016.07.015 |
| Popis: | Introduction: The leucine-rich repeat kinase 2 (LRRK2) gene contains several variants that cause Parkinson's disease (PD) and others that modify PD risk. However, little is known about the role of LRRK2 in dementia with Lewy bodies (DLB). Aims of this study were to screen DLB patients for pathogenic LRRK2 variants and to evaluate associations between common LRRK2 variants and risk of DLB. Methods: 417 clinical DLB patients and 1790 controls were included in the primary analysis. Additionally, 355 Lewy body disease patients assessed as having a high likelihood of clinical DLB based on neuropathological findings were included in secondary analysis. Seven pathogenic LRRK2 variants were assessed in patients, while 17 common LRRK2 exonic variants and 1 GWAS-nominated common LRRK2 PD-risk variant were evaluated for association with DLB. Results: We identified carriers of 2 different pathogenic LRRK2 variants. One clinical DLB patient was a p.G2019S carrier, while in the pathological high likelihood DLB series there was one carrier of the p.R1441C mutation. However, examination of clinical records revealed the p.R1441C carrier to have PD with dementia. Evaluation of common variants did not reveal any associations with DLB risk after multiple testing adjustment. However, a non-significant trend similar to that previously reported for PD was observed for the protective p.N551K-R1398H-K1423K haplotype in the clinical DLB series (OR: 0.76, P = 0.061). Conclusion: LRRK2 does not appear to play a major role in DLB, however further study of p.G2019S and the p.N551K-R1398H-K1423K haplotype is warranted to better understand their involvement in determining DLB risk. (C) 2016 Elsevier Ltd. All rights reserved. |
| Databáze: | OpenAIRE |
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