No relationship betweenTaq1 a polymorphism of dopamine D2 receptor gene and extrapyramidal adverse effects of selective dopamine D2 antagonists, bromperidol, and nemonapride in schizophrenia: A preliminary study

Mihara, Kazuo; Suzuki, Akihito; Kondo, Tsuyoshi; Nagashima, Udai; Ono, Shingo; Otani, Koichi; Kaneko, Sunao

doi:10.1002/1096-8628(20000612)96:3<422::aid-ajmg35>3.0.co;2-5

Cited by 34 publications

(14 citation statements)

References 16 publications

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“…Furthermore, no significant association between these polymorphisms and the intensity of the different types of EPS was noted, suggesting genetic variations in the DRD2 gene were not major predictors of the EPS resulting from antipsychotic treatment. This finding is similar to that of another study that demonstrated no significant differences in the incidence or severity of EPS, comparing subjects with and without the A1 allele of the DRD2 polymorphism [Mihara et al, 2000b]. Regarding the enzymes involved in the antipsychotic metabolism, three recent studies have found polymorphisms of various CYP2D6 are associated with EPS susceptibility [Jaanson et al, 2002;Schillevoort et al , 2002;Inada et al, 2003].…”

Section: Antipsychotic-induced Extrapyramidal Syndromessupporting

confidence: 90%

Pharmacogenetic Studies of Psychotropic Drug-Induced Adverse Effects

Tsai¹

2005

CPG

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Psychotropic drugs, like antipsychotics, antidepressants, mood stabilizers and anxiolytics, are effective for alleviation of certain psychiatric symptoms, however, the adverse-effects (AEs) associated with these psychotic medications may limit their use, and even cause serious outcomes. Individual differences in psychotropic-related AEs suggest that genetic components may play a major role. During the past 10-15 years, dramatic advances in molecular biology have led to the modern era of pharmacogenetics, with variability in drug response, which includes both therapeutic benefits and AEs, attributed to genetic factors discovered in different populations. Thus, identification of the genetic variations that influence drug-related AEs will facilitate pre-treatment selection and development of drugs that are safe for individual patients, based on their idiosyncratic pharmacogenetic profile. We review recent pharmacogenetic investigations of psychotropic-related AEs, proposing several recommendations for future study of psychotropic-induced AEs.

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Section: Antipsychotic-induced Extrapyramidal Syndromessupporting

confidence: 90%

Pharmacogenetic Studies of Psychotropic Drug-Induced Adverse Effects

Tsai¹

2005

CPG

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“…On the other hand, previous studies have demonstrated that subjects with one or two A1 alleles of the DRD2 polymorphism at the Taq1 A locus present lower DRD2 density than those with no A1 allele [76]. Also, other studies have shown that female patients with the A1 allele exhibit greater prolactin response to nemonapride, a selective antagonist for D2-like dopamine receptors in schizophrenic patients [77]. Due to this association between TaqI and schizophrenia, the A1 allele has been suggested to diminish dopaminergic activity in the central nervous system [78].…”

Section: Discussionmentioning

confidence: 99%

The role of C957T, TaqI and Ser311Cys polymorphisms of the DRD2 gene in schizophrenia: systematic review and meta-analysis

et al. 2016

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BackgroundThe association between the dopamine D2 receptor (DRD2) gene and schizophrenia has been studied though no conclusive outcomes have been attained. The aim of this study was to perform a systematic review and meta-analysis to explore the relation between three polymorphisms of the DRD2 gene (C957T, TaqI and Ser311Cys) and schizophrenia.MethodsThe search was made in PubMed and EBSCO databases (up to February 2016). The systematic review included 34 case–control association studies (34 for C957T, 16 for TaqI and 36 for Ser311Cys). The association analysis comprised the allelic, additive, dominant, and recessive genetic models. The meta-analysis was performed following the preferred reporting items for systematic reviews and meta-analyses (PRISMA) statement.ResultsThe meta-analysis showed that TaqI (additive model: OR 0.57, 95% CI 0.30–1.14) and C957T (additive model: OR 0.75, 95% OR 0.58–0.97, recessive model: OR 0.79, 95% CI 0.64–0.98) exert a protective effect against developing schizophrenia. However, the sub-analysis for the C957T variant showed that this polymorphism exhibits a risk factor effect on Chinese individuals (allelic model: OR 1.33, 95% CI 1.04–1.70).ConclusionOur meta-analysis suggests an association of the DRD2 gene and the risk for schizophrenia, given that TaqI and C957T polymorphisms presented a protective effect against schizophrenia, and in the sub-analyses the C957T variant increased the risk for this disorder in the Chinese population.Electronic supplementary materialThe online version of this article (doi:10.1186/s12993-016-0114-z) contains supplementary material, which is available to authorized users.

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“…37 Moreover, these patients showed a better therapeutic response. 20 However, in agreement with Mihara et al 38 we could not find a significant association between adverse events measured by the EPS-score and the TaqIA 1 allele.…”

Section: Discussionmentioning

confidence: 99%

Relationship between adverse effects of antipsychotic treatment and dopamine D2 receptor polymorphisms in patients with schizophrenia

Kaiser

Klufmöller

et al. 2002

Mol Psychiatry

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Extrapyramidal adverse symptoms (EPS) represent a major type of adverse events in treatment with typical antipsychotic drugs which share high affinity to the dopamine D 2 receptor (DRD2). Genetic variants of this receptor may modulate the therapeutic response and the severity of adverse symptoms of antipsychotics. We analyzed nine known polymorphisms of the DRD2 in 665 schizophrenic patients with European Caucasian ethnic background and compared the intensity of acute dystonia, extrapyramidal symptoms, akathisia, and tardive dyskinesia between carriers of different DRD2 genotypes. In a subgroup of 40 patients with most severe extrapyramidal symptoms we sequenced the coding region including the exonintron junctions of the DRD2 gene. Functionally relevant DRD2 amino acid variants (Ser 310 , Cys 311 ) were rare or were not found at all (Ala 96 ). Complete sequence analysis of sufferers from the most severe adverse effects revealed two new intronic polymorphisms and a silent polymorphism in exon 7, but no new amino acid variants beyond those which are already known. We found no significant association between these polymorphisms and the intensity of the different types of adverse neurologic effects of the antipsychotics. These results were obtained by correlating adverse events with each of the nine single nucleotide polymorphisms and by correlation with the estimated haplotypes. In conclusion, genetic variations in the DRD2 gene were no major predictors of the individually variable adverse effects from antipsychotic treatment in Caucasian schizophrenic patients.

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No relationship betweenTaq1 a polymorphism of dopamine D2 receptor gene and extrapyramidal adverse effects of selective dopamine D2 antagonists, bromperidol, and nemonapride in schizophrenia: A preliminary study

Cited by 34 publications

References 16 publications

Pharmacogenetic Studies of Psychotropic Drug-Induced Adverse Effects

Pharmacogenetic Studies of Psychotropic Drug-Induced Adverse Effects

The role of C957T, TaqI and Ser311Cys polymorphisms of the DRD2 gene in schizophrenia: systematic review and meta-analysis

Relationship between adverse effects of antipsychotic treatment and dopamine D2 receptor polymorphisms in patients with schizophrenia

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