Age at onset in LRRK2-associated PD is modified by SNCA variants

J Mol Neurosci. 2012 Sep;48(1):245-7. doi: 10.1007/s12031-012-9820-7. Epub 2012 Jun 6.

Abstract

Mutations in the leucine-rich repeat kinase 2 (LRRK2) and α-synuclein (SNCA) genes are known genetic causes of Parkinson's disease (PD). Recently, a genetic variant in SNCA has been associated with a lower age at onset in idiopathic PD (IPD). We genotyped the SNCA polymorphism rs356219 in 84 LRRK2-associated PD patients carrying the G2019S mutation. We found that a SNCA genetic variant is associated with an earlier age at onset in LRRK2-associated PD. Our results support the notion that SNCA variants can modify the pathogenic effect of LRRK2 mutations as described previously for IPD.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Age of Onset
  • Aged
  • Female
  • Genes, Dominant / genetics
  • Genes, Recessive / genetics
  • Genetic Variation / genetics*
  • Genotype
  • Humans
  • Leucine-Rich Repeat Serine-Threonine Protein Kinase-2
  • Male
  • Middle Aged
  • Parkinson Disease / genetics*
  • Polymorphism, Single Nucleotide / genetics
  • Protein Serine-Threonine Kinases / genetics*
  • alpha-Synuclein / genetics*

Substances

  • SNCA protein, human
  • alpha-Synuclein
  • LRRK2 protein, human
  • Leucine-Rich Repeat Serine-Threonine Protein Kinase-2
  • Protein Serine-Threonine Kinases