Association of the Ser9Gly polymorphism in the dopamine D3 receptor gene with tardive dyskinesia in Korean schizophrenics

Woo, Sung‐Il; Kim, Jae Won; Rha, Eugene; Han, Sang Hoon; Hahn, Kyu-Hee; Park, Chul‐Soo; Sohn, Jin-Wook

doi:10.1046/j.1440-1819.2002.01038.x

Cited by 47 publications

(17 citation statements)

References 33 publications

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“…Ten studies reported experiences of typical antipsychotic use in their study populations, while three studies did not specify types of antipsychotic. Four studies had genotype counts of 2 or smaller in the cross-classification of TD by genotype cell [Steen et al, 1997;Liao et al, 2001;Woo et al, 2002;Zhang et al, 2003]. In the sensitivity analysis, the meta-analytic results were very similar across the different approaches to smoothing or continuity correction [Sweeting et al, 2004].…”

Section: Description Of Studiesmentioning

confidence: 91%

The DRD3 rs6280 polymorphism and prevalence of tardive dyskinesia: A meta‐analysis

Tsai

North

West

et al. 2009

American J of Med Genetics Pt B

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To elucidate a widely suspected but inconclusive association between rs6280 in the dopamine receptor 3 gene (DRD3) and prevalence of tardive dyskinesia (TD), we conducted a meta-analysis of studies obtained in a systematic search of several bibliographic systems. We conducted several analyses of funnel plot asymmetry, overall heterogeneity, and study characteristics in analyses analogous to general, dominant and recessive inheritance models with the prevalence odds ratio (POR) as the measure of association. Thirteen eligible studies were identified with publication dates between 1997 and 2008. Evidence of funnel plot asymmetry was discerned in the dominant and general model analyses, but not in the recessive model analysis. Stratified analyses indicated that publication year, TD assessment method (Schooler-Kane criteria or other) and TD assessment frequency (single or repeated) were important study characteristics associated with heterogeneous PORs across studies. Studies conducted among patients with older age, fewer women or European (compared with Asian) ancestry reported stronger average PORs. Summary POR estimates under the dominant and general inheritance models were not warranted due to funnel plot asymmetry and heterogeneity. Under the recessive model, the summary estimate was POR = 0.93 (95% confidence interval: 0.70-1.23). We conclude that there is no or little association between DRD3 rs6280 polymorphisms and prevalence of TD.

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Section: Description Of Studiesmentioning

confidence: 91%

The DRD3 rs6280 polymorphism and prevalence of tardive dyskinesia: A meta‐analysis

Tsai

North

West

et al. 2009

American J of Med Genetics Pt B

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“…87,176,289 Polymorphisms in D3 receptors were first reported to contribute to drug-induced TD by Steen et al 230 and by Segman et al 231 In both studies, individuals with one or two copies of the Gly allele of a D 3 Ser9Gly polymorphism were more likely to develop TD with antipsychotic treatment. Several subsequent studies failed to replicate this finding, 204,232-234 but a combined study of 780 patients of different ethnic background, 235 and further reports of association in the United States, Chinese and Korean patients 221,236,237 confirm the validity and strength of this finding. The Gly variant is reportedly associated with significantly higher dopamine activity, which in turn could explain the association with movement disorders.…”

Section: Prediction Of Side Effectsmentioning

confidence: 93%

Pharmacogenetics and pharmacogenomics of schizophrenia: a review of last decade of research

2007

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The last decade of research into the pharmacogenetics of antipsychotics has seen the development of genetic tests to determine the patients' metabolic status and the first attempts at personalization of antipsychotic treatment. The most significant results are the association between drug metabolic polymorphisms, mainly in cytochrome P450 genes, with variations in drug metabolic rates and side effects. Patients with genetically determined CYP2D6 poor metabolizer (PMs) status may require lower doses of antipsychotic. Alternatively, CYP2D6 ultrarapid matabolizers (UMs) will need increased drug dosage to obtain therapeutic response. Additionally, polymorphisms in dopamine and serotonin receptor genes are repeatedly found associated with response phenotypes, probably reflecting the strong affinities that most antipsychotics display for these receptors. In particular, there is important evidence suggesting association between dopamine 2 receptor (D2) polymorphisms (Taq I and À141-C Ins/Del) and a dopamine 3 receptor (D3) polymorphism (Ser9Gly) with antipsychotic response and drug-induced tardive dyskinesia. Additionally, there is accumulating evidence indicating the influence of a 5-HT2C polymorphism (À759ÀT/C) in antipsychotic-induced weight gain. Application of this knowledge to clinical practice is slowly gathering pace, with pretreatment determination of individual's drug metabolic rates, via CYP genotyping, leading the field. Genetic determination of patients' metabolic status is expected to bring clinical benefits by helping to adjust therapeutic doses and reduce adverse reactions. Genetic tests for the pretreatment prediction of antipsychotic response, although still in its infancy, have obvious implications for the selection and improvement of antipsychotic treatment. These developments can be considered as successes, but the objectives of bringing pharmacogenetic and pharmacogenomic research in psychiatric clinical practice are far from being realized. Further development of genetic tests is required before the concept of tailored treatment can be applied to psychopharmatherapy. This review aims to summarize the key findings from the last decade of research in the field. Current knowledge on genetic prediction of drug metabolic status, general response and drug-induced side effects will be reviewed and future pharmacogenomic and epigenetic research will be discussed.

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“…In addition, a number of studies suggest a relationship to tardive dyskinesia, sex, and the age of onset. Especially the relationship to tardive dyskinesia was shown nicely in a number of studies (Steen et al, 1997;Basile et al, 1999;Segman et al, 1999;Woo et al, 2002). Since there have been also negative findings (Rietschel et al, 2000) it is important to note that in a recent study investigating a large pooled sample of 780 patients drawn from six research centers, a significant association of the DRD3 genotype with tardive dyskinesia was described (Lerer et al, 2002).…”

Section: Introductionmentioning

confidence: 89%

A Ser9Gly Polymorphism in the Dopamine D3 Receptor Gene (DRD3) and Event-Related P300 Potentials

Mulert¹,

Juckel²,

Giegling³

et al. 2006

Neuropsychopharmacol

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An important reason for the interest in P300 event-related potentials are findings in patients with psychiatric disorders like schizophrenia or alcoholism in which attenuations of the P300 amplitude are common findings. The P300 wave has been suggested to be a promising endophenotype for genetic research since attenuations of the amplitude and latency can be observed not only in patients but also in relatives. In parallel, the search for genes involved in the pathogenesis of psychiatric disorders has revealed for both, schizophrenia and alcoholism an association with a DRD3 Ser9Gly polymorphism in a number of studies. In the present study, we have investigated 124 unrelated healthy subjects of German descent and have found diminished parietal and increased frontal P300 amplitudes in Gly9 homozygotes in comparison to Ser9 carriers. This finding suggests a possible role of the DRD3 receptor gene in the interindividual variation of P300 amplitudes. Further studies should address the direct role of the DRD3 Ser9Gly polymorphism in attenuated P300 amplitudes in psychiatric disorders like schizophrenia or alcoholism.

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Association of the Ser9Gly polymorphism in the dopamine D3 receptor gene with tardive dyskinesia in Korean schizophrenics

Cited by 47 publications

References 33 publications

The DRD3 rs6280 polymorphism and prevalence of tardive dyskinesia: A meta‐analysis

The DRD3 rs6280 polymorphism and prevalence of tardive dyskinesia: A meta‐analysis

Pharmacogenetics and pharmacogenomics of schizophrenia: a review of last decade of research

A Ser9Gly Polymorphism in the Dopamine D3 Receptor Gene (DRD3) and Event-Related P300 Potentials

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