Association of the DRD2 and DRD3 polymorphisms with response to pramipexole in Parkinson's disease patients.
OBJECTIVE
To evaluate the impact of the DRD2 TaqIA and DRD3 Ser9Gly polymorphisms on the efficacy of pramipexole in treating patients with Parkinson's disease (PD).


METHODS
Thirty patients with PD prospectively received pramipexole 0.25 mg three times daily for 2 months. Unified Parkinson Disease Rating Scale (UPDRS) assessments were conducted at baseline and 2 months after treatment initiation. Improvement by 20% or more in the total score on the UPDRS was considered to indicate responsiveness. The PCR-restriction fragment length polymorphism analysis was used to analyze the DRD2 Taq1A and DRD3 Ser9Gly genotype.


RESULTS
The DRD2 Taq1A allele frequencies were A141.7 (A1) and 58.3% (A2), and the DRD3 Ser9Gly allele frequencies were 68.3 (Ser) and 31.7% (Gly). When the subjects were grouped by the DRD3 Ser9Gly polymorphism, the response rates for pramipexole treatment were significantly higher in the Ser/Ser group (60%) than in the group containing the Gly allele (13%). There was a significant association between the DRD3 Ser9Gly polymorphism and response rate to pramipexole in PD patients (P = 0.024). When the subjects were grouped by the DRD2 Taq1A polymorphism, there were no significant differences among the three Taq1A genotypes.


CONCLUSIONS
DRD3 Ser9Gly polymorphisms are significantly associated with the therapeutic efficacy of pramipexole in Chinese patients with PD. A large-scale and multi-dose group study in patients with PD is necessary for evaluating the impact of the genetic polymorphisms of the dopamine receptor on the therapeutic effects of pramipexole.
Liu
Ying-Zi
YZ
Pharmacogenetics Research Institute, Institute of Clinical Pharmacology, Central South University, Changsha, Hunan, 410078, China.
Tang
Bei-Sha
BS
Yan
Xin-Xiang
XX
Liu
Jie
J
Ouyang
Dong-Sheng
DS
Nie
Li-Nuo
LN
Fan
Lan
L
Li
Zhi
Z
Ji
Wei
W
Hu
Dong-Li
DL
Wang
Dan
D
Zhou
Hong-Hao
HH
D000368:Aged; D000483:Alleles; D044466:Asian People / Q000706:statistics & numerical data; D052160:Benzothiazoles / Q000627:therapeutic use*; D004247:DNA / Q000097:blood / Q000235:genetics / Q000302:isolation & purification; D018491:Dopamine Agonists / Q000627:therapeutic use*; D004334:Drug Administration Schedule; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D010300:Parkinson Disease / Q000188:drug therapy*; D011110:Polymorphism, Genetic; D000077487:Pramipexole; D017448:Receptors, Dopamine D2 / Q000235:genetics*; D050637:Receptors, Dopamine D3 / Q000235:genetics*; D016896:Treatment Outcome
D052160:Benzothiazoles; D018491:Dopamine Agonists; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; D000077487:Pramipexole; D004247:DNA