Association Analysis of the Dopamine D3 Receptor Gene ser9gly and Brain-Derived Neurotrophic Factor Gene val66met Polymorphisms With Antipsychotic-Induced Persistent Tardive Dyskinesia and Clinical Expression in Chinese Schizophrenic Patients

Liou, Ying‐Jay; Liao, Ding-Lieh; Chen, Jen-Yeu; Wang, Daqing; Lin, Chao-Cheng; Bai, Ya‐Mei; Yu, Shun-Chieh; Lin, Ming‐Wei; Lai, I-Ching

doi:10.1385/nmm:5:3:243

Cited by 65 publications

(37 citation statements)

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“…However, the modest ORs also suggest further contribution of other genes in the development of this severe side effect. In a somewhat surprising result, Liou et al 203 found no association between the D3 Ser9Gly polymorphism and TD in 216 Chinese schizophrenic patients (uncorrected for age), but reported association with heterozygosity for a BDNF Val66Met polymorphism. Srivastava et al 204 also failed to find association between D3 polymorphism and TD, but reported association between COMT, the enzyme that controls dopamine turnover, and TD, a finding not confirmed by other independent studies.…”

Section: Prediction Of Side Effectsmentioning

confidence: 95%

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: 95%

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

2007

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“…The super family of GPCRs contribute in many psychiatric and neuropsychiatric illnesses (28,29). Among the GPCRs, the eminent role of DRD3 in etiology and therapeutic response of many of these disorders has been frequently reported (8,(30)(31)(32). However, except a few studies (8,33) not much has been conveyed regarding autism.…”

Section: Discussionmentioning

confidence: 99%

DRD3 Ser9Gly Polymorphism and Its Influence on Risperidone Response in Autistic Children

2017

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-PURPOSE:Autism, a neuropsychiatric illness, is a complex ailment of mainly indefinite cause. Although precise pathophysiological mechanism is unclear but the role of genetics is undeniable therefore pharmacogenetics may assist to a better management of symptoms. Risperidone is widely used in autism. Considering the significance of dopaminergic system in psychological and neurological diseases and its association with autism, the hypothesis that genetic variant of dopamine receptor (DRD3), Ser9Gly (rs6280), may influence treatment of autism may be assumed. METHOD: In the present study, 56 autistic Persian children within the age range of 2.5 to 14 years were included. Diagnosis of autism was based on DSM-V criteria and the severity degree was measured by ABC-C checklists at base line and after 8 weeks of treatment with risperidone. Based on their scores patients were categorized as responsive and non-responsive groups. DRD3 Ser9Gly (rs6280) was determined by PCR-RFLP. RESULTS: Carriers of Gly allele as well as carriers of Gly/Gly and Ser/Gly genotypes showed significantly better response to risperidone compared with carriers of Ser allele and Ser/Ser genotype (P=0.027; OR= 4.18; 95%CI=1.16-15.03 and P=0.014; OR=6.825; 95%CI=1.36-34.13). CONCLUSION: Our results advocate the possible influence of genetic variation of DRD3 in clinical response to antipsychotics like risperidone in autistic individuals.

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“…Existen varios genes candidatos (COMT, CYP1A2, CYP3A4, D2, D3, 5-HT2A, 5-HT2C, …), que se han localizado como posibles responsables, si bien no hay ningún estudio totalmente concluyente al respecto 145,146,147 .…”

Section:  Discinesia Tardíaunclassified

Factores determinantes del riesgo metabólico en el tratamiento con antipsicóticos atípicos

Pato¹,

Rodríguez²,

Valverde³

2016

Psiquiatría Biológica

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Desde hace años se ha constatado que la esquizofrenia y otros trastornos psicóticos se asocian a elevadas tasas de morbimortalidad. Las causas de este incremento van desde las asociadas al uso de tratamientos específicos para esta enfermedad como a factores de salud relacionados con dicho proceso.Las principales causas de muerte en personas con enfermedad mental grave son similares a las observadas en la población general. Así, en la población general, la enfermedad cardiovascular es la principal causa de mortalidad y dicha mortalidad se ha reducido en los últimos años debido a las mejoras tratamientos y a las iniciativas de salud pública. Sin embargo, la enfermedad cardiovascular aún es alta en personas con enfermedad mental grave y en ellas no se ha visto esta reducción 1 .Los pacientes con esquizofrenia tienen una esperanza de vida un 20% menor que la población general, calculándose que mueren una media de 25 años antes 2 . Se calcula un riesgo relativo de 7,5 veces superior a la población general para la mortalidad por causas no naturales, como suicidio o muerte accidental (40% de las muertes prematuras en estos pacientes); y de 2,41 veces para la mortalidad por causas naturales, especialmente enfermedades cardiovasculares, infecciosas, respiratorias, y endocrinas 3 (60% de las muertes prematuras en estos pacientes) calculándose una mortalidad general 2-3 veces superior que en la población general 4 .En estudios que abordan específicamente las causas de muerte en la esquizofrenia frente a la población general establecen las siguientes cifras: un riesgo 2,7 veces mayor en la diabetes, un riesgo 2,3 veces mayor para enfermedades cardiovasculares, un riesgo de 3,2 veces mayor para las enfermedades respiratorias y de un 3,4 para enfermedades infecciosas 5 .En general, la mayor mortalidad cardiovascular asociada a la esquizofrenia, la depresión unipolar y el trastorno bipolar se atribuye a un riesgo relativo a presentar factores de riesgo modificables de enfermedad cardiovascular de 1 a 5 veces superior al del resto de la población 6 , tal y como se aprecia en la tabla 1.

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Association Analysis of the Dopamine D3 Receptor Gene ser9gly and Brain-Derived Neurotrophic Factor Gene val66met Polymorphisms With Antipsychotic-Induced Persistent Tardive Dyskinesia and Clinical Expression in Chinese Schizophrenic Patients

Cited by 65 publications

References 41 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

DRD3 Ser9Gly Polymorphism and Its Influence on Risperidone Response in Autistic Children

Factores determinantes del riesgo metabólico en el tratamiento con antipsicóticos atípicos

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