Association of DRD2 polymorphisms and chlorpromazine-induced extrapyramidal syndrome in Chinese schizophrenic patients1

Abstract

Aim: Extrapyramidal syndrome (EPS) is most commonly affected by typical antipsychotic drugs that have a high affinity with the D2 receptor. Recently, many research groups have reported on the positive relationship between the genetic variations in the DRD2 gene and the therapeutic response in schizophrenia patients as a result of the role of variations in the receptor in modulating receptor expression. In this study, we evaluate the role DRD2 plays in chlorpromazineinduced EPS in schizophrenic patients. Methods: We identified seven SNP(single nucleotide polymorphism) TaqIB, TaqID, Ser311Cys, rs6275, rs6277 and TaqIA) in the DRD2 gene in 146 schizophrenic inpatients (59 with EPS and 87 without EPS according to the Simpson-Angus Scale) treated with chlorpromazine after 8 weeks. The alleles of all loci were determined by PCR (polymerase chain reaction) . Results: Polymorphisms TaqID, Ser311Cys and rs6277 were not polymorphic in the population recruited in the present study. No statistical significance was found in the allele distribution of -141Cins>del, TaqIB, rs6275 and TaqIA or in the estimated haplotypes (constituted by TaqIB, rs6275 and TaqIA) in linkage disequilibrium between the two groups. Conclusion: Our results did not lend strong support to the view that the genetic variation of the DRD2 gene plays a major role in the individually variable adverse effect induced by chlorpromazine, at least in Chinese patients with schizophrenia. Our results confirmed a previous study on the relationship between DRD2 and EPS in Caucasians.

Pharmacogenetics of parkinsonism, rigidity, rest tremor, and bradykinesia in African‐Caribbean inpatients: Differences in association with dopamine and serotonin receptors

“…Notably, our data do not support the view that genetic variations of the DRD2 gene significantly predispose to AIPwhen measured as a total syndrome-and hence do replicate findings of three other studies in German [Kaiser et al, 2002] and Asian [Chong et al, 2003;Wu et al, 2006] patients, respectively. However, we do find a significant association between rigidity and the DRD2 promoter variant -141CIns/ Del, which-although debated [Pohjalainen et al, 1999;Ritchie and Noble, 2003]-has been suggested to be functional [Arinami et al, 1997;Jonsson et al, 1999] or in linkage disequilibrium with another functional polymorphism [Duan et al, 2003].…”

“…Studies focusing on HTR2A and HTR2C pharmacogenetics and AIP are currently scarce [Hamdani et al, 2005;Gunes et al, 2007]. Furthermore, there are currently only a few studies evaluating extensive sets of DRD2-polymorphisms in connection with AIP [Kaiser et al, 2002;Nakazono et al, 2005;Wu et al, 2006] and none were conducted in Negroid patients.…”

Association of two DRD2 gene polymorphisms with acute and tardive antipsychotic-induced movement disorders in young Caucasian patients

“…This study also reports an association between TaqI_D and akathisia. This intronic SNP has previously only been investigated for tardive dyskinesia (Kaiser et al 2002;Wu et al 2006;Zai et al 2007) and was significantly associated in a two-marker haplotype with C939T (Zai et al 2007). Although the pathophysiology of akathisia is still largely unknown, there is clinical evidence that medication interfering with the dopamine system and leading to a low dopaminergic tone is associated with the insistent feeling of restlessness and the urge to move Marsden and Jenner 1980).…”

DRD2/ANKK1 Taq1A (rs 1800497 C>T) genotypes are associated with susceptibility to second generation antipsychotic-induced akathisia

“…This polymorphism may alter substrate-binding specificity (Neville, 2004). Most studies that have investigated genetic variants of the DRD2/ANKK 1 Taq1A polymorphism find that there is no association with EPS, in patients who were treated with first generation antipsychotics (FGAs) (Kaiser et al, 2002;Wu et al, 2006). Only one single study reports a positive association (Güzey et al, 2007).…”