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No Evidence for an Association between Dopamine D2 Receptor Polymorphisms and Tardive Dyskinesia in Korean Schizophrenia Patients.

ABSTRACT: OBJECTIVE:Tardive dyskinesia (TD) is a long-term adverse effect of antipsychotic. Dopaminergic activity in the nigrostriatal system have been proposed to be involved in development of TD and dopamine D2 receptors (DRD2) has been regarded as a candidate gene for TD because the antipsychotics have potent antagonism DRD2. This study was aimed to find the relationship between DRD2 gene and antipsychotic-induced TD. METHODS:We evaluated whether 5 DRD2 single nucleotide polymorphisms (-141Cins>del/TaqID/NcoI/Ser311Cys/TaqIA) are associated with antipsychotic-induced TD in 263 Korean schizophrenia patients with (n=100) and without TD (n=163) who were matched for antipsychotic drug exposure and other relevant variables. Haplotype analyses were also performed. RESULTS:None of 5 polymorphisms were found to be significantly associated with TD and with TD severity as measured by Abnormal Involuntary Movement Scale. Overall haplotype (-141Cins>del/TaqID/NcoI/Ser311Cys/TaqIA) frequency was also not significantly different between TD and non-TD groups, although one rare haplotype (I-D1-T-G-A1) showed significantly different frequency between TD and non-TD groups (2.7% vs. 8.5%, respectively, p=0.031). CONCLUSION:The present study does not support that DRD2 gene may be involved in TD in the Korean population, although further studies are warranted.

SUBMITTER: Park YM

PROVIDER: S-EPMC3079185 | biostudies-literature | 2011 Mar

REPOSITORIES: biostudies-literature

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No Evidence for an Association between Dopamine D2 Receptor Polymorphisms and Tardive Dyskinesia in Korean Schizophrenia Patients.

Park Young-Min YM Kang Seung-Gul SG Choi Jung-Eun JE Kim Yong-Ku YK Kim Seung-Hyun SH Park Ji-Young JY Kim Leen L Lee Heon-Jeong HJ

Psychiatry investigation 20110310 1

<h4>Objective</h4>Tardive dyskinesia (TD) is a long-term adverse effect of antipsychotic. Dopaminergic activity in the nigrostriatal system have been proposed to be involved in development of TD and dopamine D2 receptors (DRD2) has been regarded as a candidate gene for TD because the antipsychotics have potent antagonism DRD2. This study was aimed to find the relationship between DRD2 gene and antipsychotic-induced TD.<h4>Methods</h4>We evaluated whether 5 DRD2 single nucleotide polymorphisms (- ...[more]

PMID: 21519536

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Project description:BackgroundDopamine-?-hydroxylase (DBH, EC 1.14.17.1), which converts dopamine to norepinephrine, is a candidate gene in neuropsychiatric diseases.AimTo assess the effect of regulatory variants in DBH on schizophrenia and its endophenotypes -cognition and tardive dyskinesia.MethodsWe tested association of functional variants 19bp Ins/Del, rs1989787 and rs1611115 in DBH with i) schizophrenia (1236 cases, 1136 controls), ii) tardive dyskinesia (83 positive, 162 negative) and iii) performance functions of cognition (357 cases, 306 controls) estimated by the Penn Computerized Neurocognitive Battery.ResultsA modest haplotypic (Ins-C; 19bp Ins/Del - rs1989787 C>T; p=0.04) association was observed with schizophrenia. We observed ~39% reduction in activity of 19bp Del allele on luciferase assay. Analysis of covariance revealed interactions of tardive dyskinesia status and: i) 19bp Ins/Del (genotypic, p=0.04) and ii) rs1989787 and rs1611115 (combined genotypic, p=0.004) on Abnormal Involuntary Movement Scale total score. Association of rs1611115 with positive and negative syndrome scale (PANSS) total score (p=0.05) and allelic/genotypic association with lower positive (p=0.03/0.04), general psychopathology (p=0.01/0.01) PANSS scales in tardive dyskinesia-positive; and allelic/genotypic (p=0.02/0.05) with higher score of depressive factors in tardive dyskinesia-negative subgroups were observed. Analysis of covariance with continuous variable of cognition showed interaction of health status with: i) rs1989787 on accuracy and efficiency (p=0.03) of abstraction and mental ?exibility; ii) rs1611115 on accuracy of working memory and emotion (p=0.05); iii) 19bp Ins/Del on processing speed of emotion (p=0.03). Allelic/genotypic association of rs1989787 with spatial ability (p=0.02-0.05) among healthy controls; association of rs1611115 with Global Assessment Scale scores in the past month (p=0.05) among schizophrenia subjects of cognition cohort was also observed.ConclusionsWith modest genotype-phenotype correlations available for DBH variants, personalized treatment regimens based on DBH activity for ameliorating tardive dyskinesia and cognitive symptoms may be plausible.

Project description:BackgroundTardive dyskinesia (TD) is a common side effect of antipsychotic treatment. This movement disorder consists of orofacial and limb-truncal components. The present study is aimed at investigating the role of serotonin receptors (HTR) in modulating tardive dyskinesia by genotyping patients with schizophrenia.MethodsA set of 29 SNPs of genes of serotonin receptors HTR1A, HTR1B, HTR2A, HTR2C, HTR3A, HTR3B, and HTR6 was studied in a population of 449 Caucasians (226 females and 223 males) with verified clinical diagnosis of schizophrenia (according to ICD-10: F20). Five SNPs were excluded because of low minor allele frequency or for not passing the Hardy-Weinberg equilibrium test. Affinity of antipsychotics to 5-HT2 receptors was defined according to previous publications. Genotyping was carried out with SEQUENOM Mass Array Analyzer 4.ResultsStatistically significant associations of rs1928040 of HTR2A gene in groups of patients with orofacial type of TD and total diagnosis of TD was found for alleles, and a statistical trend for genotypes. Moreover, statistically significant associations were discovered in the female group for rs1801412 of HTR2C for alleles and genotypes. Excluding patients who used HTR2A, respectively, HTR2C antagonists changed little to the associations of HTR2A polymorphisms, but caused a major change of the magnitude of the association of HTR2C variants. Due to the low patient numbers, these sub-analyses did not have significant results.ConclusionWe found significant associations in rs1928040 of HTR2A and for rs1801412 of X-bound HTR2C in female patients. The associations were particularly related to the orofacial type of TD. Excluding patients using relevant antagonists particularly affected rs1801412, but not rs1928040-related associations. This suggest that rs1801412 is directly or indirectly linked to the functioning of HTR2C. Further study of variants of the HTR2C gene in a larger group of male patients who were not using HTR2C antagonists is necessary in order to verify a possible functional role of this receptor.

Dataset Information

No Evidence for an Association between Dopamine D2 Receptor Polymorphisms and Tardive Dyskinesia in Korean Schizophrenia Patients.

Publications

No Evidence for an Association between Dopamine D2 Receptor Polymorphisms and Tardive Dyskinesia in Korean Schizophrenia Patients.

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