Differential genetic susceptibility in diphasic and peak-dose dyskinesias in Parkinson's disease

Mov Disord. 2011 Jan;26(1):73-9. doi: 10.1002/mds.23400. Epub 2010 Oct 13.

Abstract

To examine whether there is a differential genetic susceptibility in the diphasic and peak-dose forms of levodopa-induced dyskinesias (LID) in patients with Parkinson's disease (PD). The study cohort comprised 503 unrelated Korean PD patients who were treated with levodopa and had a disease duration of at least 5 years. The presence of LID was identified during a routine follow-up and special care was taken to separate the two distinct forms of LID into diphasic and peak-dose dyskinesias (PDSK). Genotyping was performed in the 503 patients and in 559 healthy controls to search for polymorphisms of DRD3 p.S9G, DRD2 Taq1A, GRIN2B c.2664C>T, c.366C>G, c.-200T>G, and the promoter region of SLC6A4. A total of 229 patients expressed LID (peak-dose in 205, diphasic in 57, and both in 33). The presence of diphasic dyskinesia (DDSK) was exclusively associated with the DRD3 p.S9G variant after adjusting for gender, age at PD onset, Hoehn & Yahr stage, and duration of levodopa treatment. Carrying the AA genotype was likely to shorten the onset of DDSK according to the duration of levodopa therapy (P = 0.02). The presence of PDSK was not significantly associated with any of the six genetic variants studied. There may be a genetic susceptibility in the development of DDSK in PD patients on chronic levodopa therapy, and its underlying pathophysiological mechanism might be distinct from that of PDSK.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antiparkinson Agents / adverse effects
  • Cohort Studies
  • Dyskinesia, Drug-Induced / classification*
  • Dyskinesia, Drug-Induced / etiology
  • Dyskinesia, Drug-Induced / genetics*
  • Female
  • Genetic Predisposition to Disease / genetics*
  • Genome-Wide Association Study
  • Genotype
  • Humans
  • Levodopa / adverse effects
  • Male
  • Middle Aged
  • Parkinson Disease / drug therapy
  • Parkinson Disease / genetics
  • Polymorphism, Genetic / genetics*
  • Probability
  • Receptors, Dopamine D2 / genetics
  • Receptors, N-Methyl-D-Aspartate / genetics
  • Serotonin Plasma Membrane Transport Proteins / genetics
  • Young Adult

Substances

  • Antiparkinson Agents
  • NR2B NMDA receptor
  • Receptors, Dopamine D2
  • Receptors, N-Methyl-D-Aspartate
  • SLC6A4 protein, human
  • Serotonin Plasma Membrane Transport Proteins
  • Levodopa