Format

Send to

Choose Destination
BMC Neurol. 2018 Feb 21;18(1):20. doi: 10.1186/s12883-018-1023-6.

Risk variants of the α-synuclein locus and REM sleep behavior disorder in Parkinson's disease: a genetic association study.

Author information

1
Department of Neurology, Drammen Hospital, Vestre Viken Hospital Trust, Dronninggata 21, 3004, Drammen, Norway. Kari.Anne.Bjornara@vestreviken.no.
2
Department of Neurology, Oslo University Hospital, Oslo, Norway.
3
Institute of Clinical Medicine, University of Oslo, Oslo, Norway.

Abstract

BACKGROUND:

Parkinson's disease is a heterogeneous disorder where genetic factors may underlie clinical variability. Rapid eye movement sleep behavior disorder (RBD) is a parasomnia strongly linked to synucleinopathies, including Parkinson's disease. We hypothesized that SNCA variants conferring risk of Parkinson's disease would also predispose to an RBD phenotype.

METHODS:

We assessed possible RBD (pRBD) status using the RBD screening questionnaire and investigated known susceptibility variants for Parkinson's disease located in the α-synuclein (SNCA) and tau (MAPT) gene loci in 325 Parkinson's disease patients. Associations between genetic risk variants and RBD were investigated by logistic regression, and an independent dataset of 382 patients from the Parkinson's Progression Marker Initiative (PPMI) study was used for replication.

RESULTS:

pRBD was associated with rs3756063 located in the 5' region of SNCA (two-sided p = 0.018, odds ratio 1.44). We replicated this finding in the PPMI dataset (one-sided p = 0.036, odds ratio 1.35) and meta-analyzed the results (two-sided p = 0.0032, odds ratio 1.40). The Parkinson's disease risk variant in the 3' region of SNCA and the MAPT variant showed no association with pRBD.

CONCLUSIONS:

Our findings provide proof of principle that a largely stable, dichotomous clinical feature of Parkinson's disease can be linked to a specific genetic susceptibility profile. Indirectly, it also supports the hypothesis of RBD as relevant marker for a distinct subtype of the disorder.

KEYWORDS:

Parkinson’s disease; RBD; REM sleep behavior disorder; SNCA; α-synuclein; genetics

PMID:
29466944
PMCID:
PMC5822630
DOI:
10.1186/s12883-018-1023-6
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for BioMed Central Icon for PubMed Central
Loading ...
Support Center