Association of alpha-, beta-, and gamma-Synuclein with diffuse lewy body disease.

Détails

ID Serval
serval:BIB_D3022283FDE7
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Association of alpha-, beta-, and gamma-Synuclein with diffuse lewy body disease.
Périodique
Archives of Neurology
Auteur⸱e⸱s
Nishioka K., Wider C., Vilariño-Güell C., Soto-Ortolaza A.I., Lincoln S.J., Kachergus J.M., Jasinska-Myga B., Ross O.A., Rajput A., Robinson C.A., Ferman T.J., Wszolek Z.K., Dickson D.W., Farrer M.J.
ISSN
1538-3687[electronic], 0003-9942[linking]
Statut éditorial
Publié
Date de publication
2010
Volume
67
Numéro
8
Pages
970-975
Langue
anglais
Résumé
OBJECTIVE: To determine the association of the genes that encode alpha-, beta-, and gamma-synuclein (SNCA, SNCB, and SNCG, respectively) with diffuse Lewy body disease (DLBD). DESIGN: Case-control study. Subjects A total of 172 patients with DLBD consistent with a clinical diagnosis of Parkinson disease dementia/dementia with Lewy bodies and 350 clinically and 97 pathologically normal controls.
INTERVENTIONS: Sequencing of SNCA, SNCB, and SNCG and genotyping of single-nucleotide polymorphisms performed on an Applied Biosystems capillary sequencer and a Sequenom MassArray pLEX platform, respectively. Associations were determined using chi(2) or Fisher exact tests.
RESULTS: Initial sequencing studies of the coding regions of each gene in 89 patients with DLBD did not detect any pathogenic substitutions. Nevertheless, genotyping of known polymorphic variability in sequence-conserved regions detected several single-nucleotide polymorphisms in the SNCA and SNCG genes that were significantly associated with disease (P = .05 to <.001). Significant association was also observed for 3 single-nucleotide polymorphisms located in SNCB when comparing DLBD cases and pathologically confirmed normal controls (P = .03-.01); however, this association was not significant for the clinical controls alone or the combined clinical and pathological controls (P > .05). After correction for multiple testing, only 1 single-nucleotide polymorphism in SNCG (rs3750823) remained significant in all of the analyses (P = .05-.009).
CONCLUSION: These findings suggest that variants in all 3 members of the synuclein gene family, particularly SNCA and SNCG, affect the risk of developing DLBD and warrant further investigation in larger, pathologically defined data sets as well as clinically diagnosed Parkinson disease/dementia with Lewy bodies case-control series.
Mots-clé
Aged, Aged, 80 and over, Animals, Evolution, Female, Gene Frequency, Genetic Predisposition to Disease, Genome-Wide Association Study, Genotype, Humans, Lewy Body Disease/genetics, Linkage Disequilibrium, Male, Phylogeny, Polymorphism, Single Nucleotide, alpha-Synuclein/genetics, beta-Synuclein/genetics, gamma-Synuclein/genetics
Pubmed
Open Access
Oui
Création de la notice
24/09/2010 18:45
Dernière modification de la notice
20/08/2019 16:53
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