Association of the DRD2 CAn-STR and DRD3 Ser9Gly polymorphisms with Parkinson's disease and response to dopamine agonists.

Dopamine agonists (DAs) play important roles in the treatment of Parkinson's disease (PD). Currently, it is thought that genetic variations in the genes encoding dopamine receptors (DR) are important factors in determining inter-individual variability in drug responses. To investigate the association between Dopamine receptor D type 2 (DRD2) dinucleotide short tandem repeat (CAn-STR) and Dopamine receptor D type 3 (DRD3) Ser9Gly polymorphisms and the risk of PD, as well as the possible reasons for PD patients using different doses of DAs, we recruited 168 idiopathic PD patients and 182 controls. There were no significant differences in DRD2 CAn-STR and DRD3 Ser9Gly genotypes (p=0.184, p=0.196) or in allele frequencies (p=0.239, p=0.290) between PD patients and controls. There was no association between DRD2 CAn-STR polymorphism and doses of DAs. Among three different DRD3 Ser9Gly genotypes (Ser/Ser, Ser/Gly, Gly/Gly), patients carrying Gly/Gly genotype used higher doses of DAs than patients with Ser/Gly and Ser/Ser genotypes (p=0.001). In pramipexole subgroup, the Gly/Gly group took more pramipexole than the other genotype groups (p<0.001), whereas the doses of piribedil were not significantly different among three genotypes (p=0.735). Our results suggest that genotype in DRD3 Ser9Gly was the main factor determining different doses of DAs and PD patients carrying Gly/Gly genotype require higher doses of pramipexole for effective treatment. This study may provide insights into understanding possible reasons for different responses to DAs in Chinese PD patients.