The GBA, DYRK1A and MS4A6A polymorphisms influence the age at onset of Chinese Parkinson patients

Neurosci Lett. 2016 May 16:621:133-136. doi: 10.1016/j.neulet.2016.04.014. Epub 2016 Apr 13.

Abstract

Parkinson's disease (PD) is known as the most common neurodegenerative disease after Alzheimer's disease (AD). The precise pathogenic mechanism of PD remains unclear, but genetic and environmental factors are widely recognized to be associated with it. Although many associated genes have been discovered, they account for only a few PD patients. Recently, there are growing evidences indicating that patients with PD and AD share similarities in clinical features, pathology and genetic risks. However, no study has been conducted on the relations between AD associated genes and age at onset (AAO) of PD. In this study, we have detected 14 single nucleotide polymorphisms (SNPs) in 9 AD genome wide association studies top hit genes and 4 SNPs in 4 PD-cognitive impairment related genes among 297 Chinese PD patients. Through the linear regression analysis, we identified the significant associations of the GBA L444P mutation and DYRK1A rs8126696 T allele with the earlier AAO in PD patients, and the A allele at MS4A6A rs610932 with the delayed AAO of PD. This is the first report of significant associations of DYRK1A and MS4A6A SNPs and the AAO of PD. On account of their effects both in AD and PD, it is indicated that AD and PD possibly share some common pathways.

Keywords: Age at onset; Alzheimer’s disease; Parkinson’s disease.

MeSH terms

  • Adult
  • Age of Onset
  • Aged
  • Aged, 80 and over
  • Asian People
  • Dyrk Kinases
  • Female
  • Genetic Predisposition to Disease
  • Genome-Wide Association Study
  • Glucosylceramidase / genetics*
  • Humans
  • Male
  • Membrane Proteins / genetics*
  • Middle Aged
  • Parkinson Disease / ethnology
  • Parkinson Disease / genetics*
  • Polymorphism, Single Nucleotide
  • Protein Serine-Threonine Kinases / genetics*
  • Protein-Tyrosine Kinases / genetics*

Substances

  • Glucosylceramidase
  • Membrane Proteins
  • Protein Serine-Threonine Kinases
  • Protein-Tyrosine Kinases
  • Dyrk Kinases
  • MS4A6A protein, human