SNCA rs11931074 polymorphism correlates with spontaneous brain activity and motor symptoms in Chinese patients with Parkinson's disease

J Neural Transm (Vienna). 2019 Aug;126(8):1037-1045. doi: 10.1007/s00702-019-02038-4. Epub 2019 Jun 26.

Abstract

The α-synuclein (SNCA) gene is thought to be involved in levels of α-synuclein and influence the susceptibility for the development of Parkinson's disease (PD). The aim of the present study is to explore the association among SNCA rs1193074 polymorphism, spontaneous brain activity and clinical symptoms in PD patients. 62 PD patients and 47 healthy controls (HC) were recruited and underwent resting-state functional magnetic resonance imaging (rs-fMRI) scans. Also blood sample of each participant was genotyped for rs11931074 polymorphism (PD: TT = 19, GT = 32, GG = 11; HC: TT = 10, GT = 25, GG = 12) and then examined to ascertain the influence of different genotypes on regional brain activity with amplitude low-frequency fluctuation analysis (ALFF). Furthermore, we evaluated the relationship among genotypes, interactive brain region and clinical symptoms in PD. Compared with HC subjects, PD patients showed decreased ALFF values in right lingual gyrus and increased ALFF values in right cerebellum posterior lobe. Significant interaction of ''groups × genotypes'' was found in the right angular gyrus, where there were higher ALFF values in TT genotype than in GT or GG genotype in the PD group and there was a contrary trend in the HC group. And further Spearman's correlative analyses revealed that ALFF values in right angular gyrus were negatively associated with unified Parkinson's disease rating scale (UPDRS) III score in PD-TT genotype. Our study shows for the first time that SNCA rs11931074 polymorphism might modulate brain functional alterations and correlate with motor symptoms in Chinese PD patients.

Keywords: Amplitude of low-frequency fluctuations (ALFF); Angular gyrus; Imaging genetics; Parkinson’s disease; SNCA rs11931074.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Brain / diagnostic imaging
  • Brain / physiopathology*
  • Brain Mapping
  • Female
  • Genetic Predisposition to Disease
  • Humans
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Parkinson Disease / diagnostic imaging
  • Parkinson Disease / genetics*
  • Parkinson Disease / physiopathology*
  • Polymorphism, Single Nucleotide*
  • Rest
  • Severity of Illness Index
  • alpha-Synuclein / genetics*

Substances

  • SNCA protein, human
  • alpha-Synuclein