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

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Abstract

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.

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Acknowledgements

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.

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Author notes

  1. M. Toffoli and E. Dreussi contributed equally to the study.

Authors and Affiliations

  1. Neurology Unit, Department of Experimental and Clinical Medical Sciences, University of Udine Medical School, Udine, Italy

    M. Toffoli, M. Valente, N. Sanvilli & G. L. Gigli

  2. Experimental and Clinical Pharmacology, Centro Di Riferimento Oncologico-National Cancer Institute, Aviano, Italy

    E. Dreussi, E. Cecchin, M. Montico, S. Gagno, M. Garziera, M. Polano & G. Toffoli

  3. Department of Neurosciences, “S. Maria della Misericordia” University Hospital, Udine, Italy

    M. Valente & G. L. Gigli

  4. Center of Sleep Disorders, Department of Basic Medical Sciences, Neurosciences and Sense Organs, University “Aldo Moro”, Bari, Italy

    M. Savarese

  5. IRCCS Institute of Neurological Sciences, Bologna and Department of Biomedical and NeuroMotor Sciences, University of Bologna, Bologna, Italy

    G. Calandra-Buonaura

  6. Neurophysiopathology Unit, Sleep Medicine Centre, Department of Systems Medicine, University of Rome Tor Vergata, Rome, Italy

    F. Placidi

  7. Unit of Sleep Medicine and Epilepsy, C. Mondino National Neurological Institute, Pavia, Italy

    M. Terzaghi

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  1. M. Toffoli
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  2. E. Dreussi
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  3. E. Cecchin
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  6. M. Montico
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  13. M. Terzaghi
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  14. G. Toffoli
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  15. G. L. Gigli
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Corresponding author

Correspondence to M. Toffoli.

Ethics declarations

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.

Funding

This work was supported by the “Associazione Italiana per la Ricerca sul Cancro” (AIRC; Special Program Molecular Clinical Oncology, 5 × 1000 [No. 12214]).

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Toffoli, M., Dreussi, E., Cecchin, E. et al. SNCA 3′UTR genetic variants in patients with Parkinson’s disease and REM sleep behavior disorder. Neurol Sci 38, 1233–1240 (2017). https://doi.org/10.1007/s10072-017-2945-2

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  • DOI: https://doi.org/10.1007/s10072-017-2945-2

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