SNCA 3′UTR genetic variants in patients with Parkinson’s disease and REM sleep behavior disorder

• Published in: Neurological sciences Vol. 38; no. 7; pp. 1233 - 1240
• Main Authors: Toffoli, M., Dreussi, E., Cecchin, E., Valente, M., Sanvilli, N., Montico, M., Gagno, S., Garziera, M., Polano, M., Savarese, M., Calandra-Buonaura, G., Placidi, F., Terzaghi, M., Toffoli, G., Gigli, G. L.
• Format: Journal Article
• Language: English
• Published: Milan Springer Milan 01-07-2017
• Subjects: Medicine; Medicine & Public Health; Neurology; Neuroradiology; Neurosurgery; Original Article; Psychiatry; Genetic variants; RBD; Parkinson’s disease; Alpha-synuclein; REM sleep behavior disorder; SNCA
• ISSN: 1590-1874; 1590-3478
• DOI: 10.1007/s10072-017-2945-2

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.