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Research Paper|Volume 12, Issue 20|pp 20880—20887

SNCA Rep1 microsatellite length influences non-motor symptoms in early Parkinson’s disease

Alisa CW Yong1, Yi Jayne Tan1, Yi Zhao2, Zhonghao Lu1, Ebonne YL Ng3, Samuel YE Ng1, Nicole SY Chia1, Xinyi Choi3, Dede Heng3, Shermyn Neo1, Zheyu Xu1, Kay Yaw Tay1, Wing Lok Au1, Eng-King Tan3,4, Louis CS Tan1, Adeline SL Ng1,4
  • 1Department of Neurology, National Neuroscience Institute, Tan Tock Seng Hospital, Singapore, Singapore
  • 2Department of Clinical Translational Research, Singapore General Hospital, Singapore, Singapore
  • 3Department of Neurology, National Neuroscience Institute, Singapore General Hospital, Singapore, Singapore
  • 4Neuroscience and Behavioural Disorders Program, Duke-NUS Medical School, Singapore, Singapore
* Co-first authors
# Co-senior authors
Received: May 7, 2020Accepted: September 9, 2020Published: October 20, 2020
https://doi.org/10.18632/aging.104111

Copyright: © 2020 Yong et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Long alpha-synuclein gene (SNCA) promoter (Rep1) allele-carriers are linked to higher risk for Parkinson’s disease (PD) and faster motor progression. Non-motor symptoms including autonomic, neuropsychiatric, and sleep disorders are common in PD. However, the relationship between SNCA Rep1 microsatellite lengths and non-motor symptoms in early PD remains to be elucidated. 171 consecutive early PD patients were recruited from tertiary clinics and genotyped for Rep1. Multivariable regression analyses were performed to examine associations between Rep1 alleles and non-motor outcome scores. Longer Rep1 alleles significantly associated with higher total Non-Motor Symptom Scale (NMSS) scores (p=.006) and Hospital Anxiety and Depression Scale (HADS) depression subscale scores (p=.002), after adjusting for covariates and Bonferroni correction. We demonstrated that SNCA Rep1 allele length influences overall non-motor symptom burden and depression in early PD patients. Further functional studies to evaluate the role of Rep1 in non-dopaminergic systems may unravel new therapeutic targets for non-motor symptoms in PD.