Our results suggest that upregulation of putamen dopamine D3 receptor and alterations along the noncanonical GRK6/β-arrestin2/Akt/GSK-3β molecular cascade are associated with the development of tardive dyskinesia in nonhuman primates.
This study investigated the possible relationship between TD and the polymorphisms Ser9Gly (DRD3), 102T>C (HTR2A), -1438G>A(HTR2A) and Cys23Ser (HTR2C) in African-Caribbean inpatients.
Thus, a number of studies have focused on the association of dopamine system gene polymorphisms and TD, with the most consistent findings being an association between TD and the Ser9Gly polymorphism of the DRD3 gene and the TaqIA site 3' of the DRD2 gene.
The primary focus has been on SNPs in dopamine and serotonin receptor genes: persuasive meta-analytic evidence exists for an effect of the dopamine D2 and D3 receptor genes (DRD2 and DRD3) in risk for tardive dyskinesia (TD) and for an effect of variation at the 5-HT2C receptor gene (HTR2C) for liability to APD-induced weight gain.
While BDNF markers showed no association, a haplotype containing rs3732782, rs905568, and rs7620754 in the 5' region of DRD3 was associated with TD diagnosis (p[10,000 permutations]=0.007).
Search for these determinants has led to a few consensus associations of CYP2D6 *10, CYP1A2*1F, DRD2 Taq1A (rs1800497), DRD3rs6280" genes_norm="1814">Ser9Gly (rs6280) and MnSOD Ala9Val (rs4880) variants with TD.
Two gene variants appeared to be significant after adding them to the clinical regression models: (1) Ser9GlyDRD3 polymorphism was associated with severe TD (odds ratio for patients with 1 mutant allele when compared with individuals with 2 wild types was 2.5, 95% confidence interval 1.1-5.6, whereas the odds ratio for patients with 2 mutant alleles when compared with individuals with 1 mutant was 2.8, 95% confidence interval 1.0-7.4), and (2) GSTM1 absence was associated with TD (odds ratio 1.7, 95% confidence interval 1.2-2.4) particularly in white women.
We performed an association study between four candidate genes, DRD2, DRD3, DRD4 and 5-HT2A for the presence of tardive dyskinesia (TD) on 84 patients with residual schizophrenia.
The association of TD with the serine/serine genotype of the DRD3 may be an epiphenomenon of patients with a subtype of schizophrenia who had more exposure to neuroleptics.
The antipsychotic adverse reaction of tardive dyskinesia and its association with the dopamine D(3) receptor will be critically examined, as well as the added influence of antipsychotic metabolism via the cytochrome P450 1A2 gene (CYP1A2 ).
Four published studies have reported an association between a serine (ser) to glycine (gly) polymorphism in exon 1 of the dopamine D3 receptor gene (DRD3) and TD; three failed to replicate this finding and one found an insignificant trend.
In conclusion, we suggest that Gly/Gly homozygotes in the MscI polymorphic site of the dopamine D3 receptor gene may cause some change in the function of the dopamine D3 receptor and may be involved the pathogenesis of TD.
We found no evidence that the dopamine D3 receptor gene is likely to confer susceptibility to the development of tardive dyskinesia in Chinese patients with schizophrenia.
Our results are in line with a previous report, the results of which suggest that the presence of the DRD3(ser-gly) genotype may be a risk factor for the development of TD in patients treated with antipsychotics.
The studies presented in this article evaluate the role of single nucleotide polymorphisms in dopamine D3 receptor (DRD3) and CYP1A2 genes for propensity to develop TD in patients with schizophrenia.
To examine the association of a functional polymorphism in the 5-HT2C receptor gene (HT2CR) with TD and the joint contribution of HT2CR and DRD3 to susceptibility.
Association of dopamine D3-receptor gene variants with neuroleptic induced akathisia in schizophrenic patients: a generalization of Steen's study on DRD3 and tardive dyskinesia.