Polymorphisms of dopamine receptors and tardive dyskinesia among Chinese patients with schizophrenia

Chong, Siow‐Ann; Tan, Ene‐Choo; Tan, Chay Hoon; Mythily,; Chan, Yiong Huak

doi:10.1002/ajmg.b.10004

Cited by 58 publications

(41 citation statements)

References 26 publications

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“…The Gly variant is reportedly associated with significantly higher dopamine activity, which in turn could explain the association with movement disorders. 238 Only one study reported the Ser/Ser genotype associated with increased risk of TD after correcting for age in a large Chinese cohort, 226 a contradiction that may be explained by different LD status in this population. A recent meta-analyses showed that the D3 Gly9 allele conferred an increased risk of developing TD (P = 0.04, O.R.…”

Section: Prediction Of Side Effectsmentioning

confidence: 96%

“…Only one report suggested association between D2 polymorphisms and TD, 229 but no evidence was found by other groups. 204,[223][224][225][226][227][228] Similarly, no association was found when investigating D1 polymorphisms and a polymorphism in the dopamine transporter (DAT) in relation to TD, 204 and no association was found between D2 and D3 polymorphisms and tardive distonia, an uncommon druginduced movement disorder, in a pilot study on nine patient sufferers. 240 Serotonin inhibition of dopamine function may also contribute to the pathological events related to movement disorders.…”

Section: Prediction Of Side Effectsmentioning

confidence: 99%

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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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Section: Prediction Of Side Effectsmentioning

confidence: 96%

Section: Prediction Of Side Effectsmentioning

confidence: 99%

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

2007

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“…Early studies did not show an association with Taq1A or other polymorphisms. [56][57][58][59][60][61] One study found a significant association between the Taq1A polymorphism of the dopamine 2 receptor gene (DRD2) and TD in female patients. 62 Another study showed an increased risk for EPS in patients with the À141C Del allele of the DRD2 gene.…”

Section: Dopamine 2 Receptormentioning

confidence: 99%

Antipsychotic-induced tardive dyskinesia and polymorphic variations in COMT, DRD2, CYP1A2 and MnSOD genes: a meta-analysis of pharmacogenetic interactions

Bakker¹,

Harten²,

2008

Mol Psychiatry

138

118

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Despite accumulating evidence pointing to a genetic basis for tardive dyskinesia, results to date have been inconsistent owing to limited statistical power and limitations in molecular genetic methodology. A Medline, EMBASE and PsychINFO search for literature published between 1976 and June 2007 was performed, yielding 20 studies from which data were extracted for calculation of pooled estimates using meta-analytic techniques. Evidence from pooled data for genetic association with tardive dyskinesia (TD) showed (1) in COMT val158met , using Val-Val homozygotes as reference category, a protective effect for Val-Met heterozygotes (OR = 0.63, 95% CI: 0.46-0.86, P = 0.004) and Met carriers (OR = 0.66, 95% CI: 0.49-0.88, P = 0.005); (2) in Taq1A in DRD2, using the A1 variant as reference category, a risk-increasing effect for the A2 variant (OR = 1.30, 95% CI: 1.03-1.65, P = 0.026), and A2-A2 homozygotes using A1-A1 as reference category (OR = 1.80, 95% CI: 1.03-3.15, P = 0.037); (3) in MnSOD Ala9Val, using Ala-Ala homozygotes as reference category, a protective effect for Ala-Val (OR = 0.37, 95% CI: 0.17-0.79, P = 0.009) and for Val carriers (OR = 0.49, 95% CI: 0.24-1.00, P = 0.047). These analyses suggest multiple genetic influences on TD, indicative of pharmacogenetic interactions. Although associations are small, the effects underlying them may be subject to interactions with other loci that, when identified, may have acceptable predictive power. Future genetic research will take advantage of new genomic knowledge.

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“…Six included the number of patients with and without TD and genotypes for Taq1A, while five included the number of TD-positive and TD-negative patients with genotypes for the À141C Ins/Del polymorphism. [2][3][4][5][6][7][8] All subjects were selected based on their diagnoses of schizophrenia or schizoaffective disorder, according to DSM-III-R or IV, using case records with or without patient interviews. The presence of TD was assessed from our study using the Abnormal Involuntary Movement Scale (AIMS) or the modified Hillside Simpson Dyskinesia Scale (HSDS) in the case of 49 patients, as described previously.…”

mentioning

confidence: 99%

Meta-analysis of two dopamine D2 receptor gene polymorphisms with tardive dyskinesia in schizophrenia patients

et al. 2007

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Polymorphisms of dopamine receptors and tardive dyskinesia among Chinese patients with schizophrenia

Cited by 58 publications

References 26 publications

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

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

Antipsychotic-induced tardive dyskinesia and polymorphic variations in COMT, DRD2, CYP1A2 and MnSOD genes: a meta-analysis of pharmacogenetic interactions

Meta-analysis of two dopamine D2 receptor gene polymorphisms with tardive dyskinesia in schizophrenia patients

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