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Genetic analysis of α‐synuclein 3′ untranslated region and its corresponding microRNAs in relation to Parkinson's disease compared to dementia with Lewy bodies
Author(s) -
Tagliafierro Lidia,
Glenn OmolaraChinue,
Zamora Madison E.,
Beach Thomas G.,
Woltjer Randy L.,
Lutz Michael W.,
ChibaFalek Ornit
Publication year - 2017
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2017.03.001
Subject(s) - synucleinopathies , dementia with lewy bodies , biology , induced pluripotent stem cell , parkinson's disease , microrna , alpha synuclein , lewy body , genetics , gene , dementia , pathology , disease , medicine , embryonic stem cell
The α‐synuclein ( SNCA ) gene has been implicated in the etiology of Parkinson's disease (PD) and dementia with Lewy bodies (DLB). Methods A computational analysis of SNCA 3′ untranslated region to identify potential microRNA (miRNA) binding sites and quantitative real‐time polymerase chain reaction (PCR) to determine their expression in isogenic induced pluripotent stem cell–derived dopaminergic and cholinergic neurons as a model of PD and DLB, respectively, were performed. In addition, we performed a deep sequencing analysis of the SNCA 3′ untranslated region of autopsy‐confirmed cases of PD, DLB, and normal controls, followed by genetic association analysis of the identified variants. Results We identified four miRNA binding sites and observed a neuronal‐type–specific expression profile for each miRNA in the different isogenic induced pluripotent stem cell–derived dopaminergic and cholinergic neurons. Furthermore, we found that the short structural variant rs777296100‐polyT was moderately associated with DLB but not with PD. Discussion We suggest that the regulation of SNCA expression through miRNAs is neuronal‐type–specific and possibly plays a part in the phenotypic heterogeneity of synucleinopathies. Furthermore, genetic variability in the SNCA gene may contribute to synucleinopathies in a pathology‐specific manner.