title: Dopamine D2 receptor gene polymorphism and the risk of levodopa-induced dyskinesias in PD.
abstract: OBJECTIVE
  To investigate whether polymorphisms in the genes for dopamine receptors D1 and D2 are associated with the risk of developing peak-dose dyskinesias in PD.
  
  
  BACKGROUND
  Peak-dose dyskinesias are the most common side effects of levodopa therapy for PD. The identified predictors may only partially account for the risk of developing peak-dose dyskinesias because a substantial proportion of patients never develop peak-dose dyskinesias. Genetic factors could play a role in determining the occurrence of peak-dose dyskinesias.
  
  
  METHODS
  A case-control study of 136 subjects with sporadic PD and 224 population control subjects. We studied three polymorphisms involving the dopamine receptor D1 gene and one intronic short tandem repeat polymorphism of the dopamine receptor D2 gene.
  
  
  RESULTS
  The polymorphisms of the dopamine receptor D1 gene were not associated with the risk of developing PD or peak-dose dyskinesias. The 15 allele of the polymorphism of the dopamine receptor D2 gene was more frequent in parkinsonian subjects than in control subjects. More important, the frequency of both the 13 allele and the 14 allele of the dopamine receptor D2 gene polymorphism was higher in nondyskinetic than in the dyskinetic PD subjects. The risk reduction of developing peak-dose dyskinesias for PD subjects carrying at least 1 of the 13 or 14 alleles was 72% with respect to the PD subjects who did not carry these alleles.
  
  
  CONCLUSIONS
  Certain alleles of the short tandem repeat polymorphism of the dopamine receptor D2 gene reduce the risk of developing peak-dose dyskinesias and could contribute to varying susceptibility to develop peak-dose dyskinesias during levodopa therapy.
authors.affiliation: Institute of Neurology, Department of Medical Sciences, University of Catanzaro, Italy.
authors.forename: R L
authors.initials: RL
authors.lastname: Oliveri
authors.forename: G
authors.initials: G
authors.lastname: Annesi
authors.forename: M
authors.initials: M
authors.lastname: Zappia
authors.forename: D
authors.initials: D
authors.lastname: Civitelli
authors.forename: R
authors.initials: R
authors.lastname: Montesanti
authors.forename: D
authors.initials: D
authors.lastname: Branca
authors.forename: G
authors.initials: G
authors.lastname: Nicoletti
authors.forename: P
authors.initials: P
authors.lastname: Spadafora
authors.forename: A A
authors.initials: AA
authors.lastname: Pasqua
authors.forename: R
authors.initials: R
authors.lastname: Cittadella
authors.forename: V
authors.initials: V
authors.lastname: Andreoli
authors.forename: A
authors.initials: A
authors.lastname: Gambardella
authors.forename: U
authors.initials: U
authors.lastname: Aguglia
authors.forename: A
authors.initials: A
authors.lastname: Quattrone
mesh_terms: D000328:Adult; D000368:Aged; D000483:Alleles; D000978:Antiparkinson Agents / Q000009:adverse effects* / Q000627:therapeutic use; D016022:Case-Control Studies; D004409:Dyskinesia, Drug-Induced; D020820:Dyskinesias / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D007980:Levodopa / Q000009:adverse effects* / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D010300:Parkinson Disease / Q000188:drug therapy / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000235:genetics*; D017448:Receptors, Dopamine D2 / Q000235:genetics*; D020080:Tandem Repeat Sequences
chemical_list: D000978:Antiparkinson Agents; D017448:Receptors, Dopamine D2; D007980:Levodopa