REM sleep behavior disorder (RBD) is an early marker of Parkinson’s disease (PD); however, it is still unclear which patients with RBD will eventually develop PD. Single nucleotide polymorphisms (SNPs) in the 3′untranslated region (3′UTR) of alpha-synuclein (SNCA) have been associated with PD, but at present, no data is available about RBD. The 3′UTR hosts regulatory regions involved in gene expression control, such as microRNA binding sites. The aim of this study was to determine RBD specific genetic features associated to an increased risk of progression to PD, by sequencing of the SNCA-3′UTR in patients with “idiopathic” RBD (iRBD) and in patients with PD. We recruited 113 consecutive patients with a diagnosis of iRBD (56 patients) or PD (with or without RBD, 57 patients). Sequencing of SNCA-3′UTR was performed on genomic DNA extracted from peripheral blood samples. Bioinformatic analyses were carried out to predict the potential effect of the identified genetic variants on microRNA binding. We found three SNCA-3′UTR SNPs (rs356165, rs3857053, rs1045722) to be more frequent in PD patients than in iRBD patients (p = 0.014, 0.008, and 0.008, respectively). Four new or previously reported but not annotated specific genetic variants (KP876057, KP876056, NM_000345.3:c*860T>A, NM_000345.3:c*2320A>T) have been observed in the RBD population. The in silico approach highlighted that these variants could affect microRNA-mediated gene expression control. Our data show specific SNPs in the SNCA-3′UTR that may bear a risk for RBD to be associated with PD. Moreover, new genetic variants were identified in patients with iRBD.
This is a preview of subscription content, log in to check access.
For their suggestions and support, the authors thank Prof. Giancarlo Logroscino and Dr. Valentina Cardinali from the Department of Basic Medical Science of the Univerity “Aldo Moro” of Bari; Dr. Raffaele Manni from the Neurological Institute “C. Mondino”; Dr. Federica Provini from the Department of Biomedical and Neuromotor Sciences of “Bellaria Hospital,” University of Bologna; and Dr. Francesca Izza from the Neurophysiopathology Unit, Sleep Medicine Centre for the University of Rome Tor Vergata.
Compliance with ethical standards
All procedures were approved by the ethical committee of each participating institution and were in accordance with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. Informed consent was obtained from all individual participants included in the study.
Conflict of interest
The authors declare that they have no conflict of interest.
This work was supported by the “Associazione Italiana per la Ricerca sul Cancro” (AIRC; Special Program Molecular Clinical Oncology, 5 × 1000 [No. 12214]).
AASM (2005) ICSD-II: International Classification of Sleep Disorders, 2nd edn (ICSD-2): diagnostic and coding manual.Google Scholar
Schenck CH, Bundlie SR, Ettinger MG, Mahowald MW (1986) Chronic behavioral disorders of human REM sleep: a new category of parasomnia. Sleep 9:293–308CrossRefPubMedGoogle Scholar
Satake W, Nakabayashi Y, Mizuta I et al (2009) Genome-wide association study identifies common variants at four loci as genetic risk factors for Parkinson’s disease. Nat Genet 41:1303–1307. doi:10.1038/ng.485CrossRefPubMedGoogle Scholar
Hadjigeorgiou GM, Xiromerisiou G, Gourbali V et al (2006) Association of alpha-synuclein Rep1 polymorphism and Parkinson’s disease: influence of Rep1 on age at onset. Mov Disord 21:534–539. doi:10.1002/mds.20752CrossRefPubMedGoogle Scholar
Mizuta I, Satake W, Nakabayashi Y et al (2006) Multiple candidate gene analysis identifies alpha-synuclein as a susceptibility gene for sporadic Parkinson’s disease. Hum Mol Genet 15:1151–1158. doi:10.1093/hmg/ddl030CrossRefPubMedGoogle Scholar
Schenck CH, Bundlie SR, Mahowald MW (1996) Delayed emergence of a parkinsonian disorder in 38% of 29 older men initially diagnosed with idiopathic rapid eye movement sleep behaviour disorder. Neurology 46:388–393CrossRefPubMedGoogle Scholar
Iranzo A, Molinuevo JL, Santamaría J et al (2006) Rapid-eye-movement sleep behaviour disorder as an early marker for a neurodegenerative disorder: a descriptive study. Lancet Neurol 5:572–577CrossRefPubMedGoogle Scholar
Postuma R, Gagnon J, Vendette M (2009) Quantifying the risk of neurodegenerative disease in idiopathic REM sleep behavior disorder. NeurologyGoogle Scholar