Cebus apella, a nonhuman primate highly susceptible to neuroleptic side effects, carries the GLY9 dopamine receptor D3 associated with tardive dyskinesia in humans

Werge, Thomas; Elbæk, Z; Andersen, Maibritt B.; Lundbæk, Jens August; Rasmussen, Henrik Berg

doi:10.1038/sj.tpj.6500152

Cited by 17 publications

(8 citation statements)

References 23 publications

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“…Lerer et al (2002) published the first pooled and meta-analysis of studies on DRD3 and TD, finding a significant association with DRD3Gly. Reports published since then further implicate DRD3 in susceptibility to TD (Chong et al, 2003 ;Werge et al, 2003 ;Woo et al, 2002).…”

Section: Introductionmentioning

confidence: 93%

Combined analysis of 635 patients confirms an age-related association of the serotonin 2A receptor gene with tardive dyskinesia and specificity for the non-orofacial subtype

Lerer¹,

Segman²,

Tan

et al. 2005

Int. J. Neuropsychopharm.

111

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Tardive dyskinesia (TD) is an important limiting factor in the use of typical antipsychotic drugs. Genetic variability in the serotonin 2A (5-HT(2A)) receptor may influence risk for TD but the results of prior studies are not confirmatory. The objective of this study was to determine association of T102C and His452Tyr polymorphisms in the 5-HT(2A) receptor gene (HTR(2A)) with TD in a large, multicentre patient sample. The design employed case-control analysis controlling for possible confounders using pooled, original data from published and available unpublished samples and employing logistic regression, analysis of variance and meta-analysis. The study sample consisted of 635 patients with schizophrenia or schizoaffective disorder (256 with TD and 379 without TD) drawn from five research centres, divided into six groups based on population origin. The main outcome measure was association of a categorical diagnosis of TD based on the Research Diagnostic Criteria for TD with HTR(2A) T102C and His452Tyr genotypes and haplotypes. The findings indicate significant association of TD with HTR(2A) T102C genotype (p=0.002) over and above the effect of population group, also when controlling for age and gender (p=0.0008), but not with His452Tyr genotype. The T102C genotype was significantly associated with TD in older (>median age 47 yr, p=0.002) but not younger patients and in patients with non-orofacial (limb-truncal) (p=0.001) but not orofacial TD. By meta-analysis the Mantel-Haenszel (M-H) pooled odds ratio (OR) across all the available data was 1.64. A T102C-His452Tyr haplotype was significantly associated with TD (p=0.0008). These findings confirm that genetic variability in HTR(2A) contributes a small but significant degree of risk for the expression of TD, particularly in older patients and specifically for the non-orofacial (limb-truncal) type. Together with other genetic variants associated with TD the findings could be used to assess risk in patients who are candidates for treatment with typical antipsychotic medications.

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Section: Introductionmentioning

confidence: 93%

Combined analysis of 635 patients confirms an age-related association of the serotonin 2A receptor gene with tardive dyskinesia and specificity for the non-orofacial subtype

Lerer¹,

Segman²,

Tan

et al. 2005

Int. J. Neuropsychopharm.

111

View full text Add to dashboard Cite

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“…These include reports on genetic association with neuroendocrine function and its role in temperament and alcohol consumption (e.g., cortiotropin-releasing hormone haplotype, Barr, Dvoskin, et al, 2008), alcohol response (mu opioid receptor gene, Barr et al, 2007), infant attachment behavior (mu opioid receptor gene, Barr, Schwandt, et al, 2008), and susceptibility to the side effects of neuroleptic drugs (dopamine 3 receptor, Werge, Elbaek, Andersen, Lundbaek, & Rasmussen, 2003). Taken together, these findings provide strong evidence that evaluation of specific genetic variation is a useful research avenue for uncovering sources of individual variation in a broad range of behavioral and biological phenotypes.…”

Section: Other Genesmentioning

confidence: 99%

Nonhuman Primate Research Contributions to Understanding Genetic and Environmental Influences on Phenotypic Outcomes across Development

Bennett

Pierre

2010

Handbook of Developmental Science, Behavior, and Genetics

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“…Ser9Gly polymorphism in DRD3 was studied extensively and inconsistent reports were published [2][3][4] . In addition, several studies have aimed to identify the relationship between the DRD2 gene polymorphisms and the drug response or adverse effects, but the results are also controversial [5][6][7] .…”

Section: Introductionmentioning

confidence: 99%

Association of DRD2 polymorphisms and chlorpromazine-induced extrapyramidal syndrome in Chinese schizophrenic patients1

Gao

Xing

et al. 2006

Acta Pharmacologica Sinica

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Aim: Extrapyramidal syndrome (EPS) is most commonly affected by typical antipsychotic drugs that have a high affinity with the D2 receptor. Recently, many research groups have reported on the positive relationship between the genetic variations in the DRD2 gene and the therapeutic response in schizophrenia patients as a result of the role of variations in the receptor in modulating receptor expression. In this study, we evaluate the role DRD2 plays in chlorpromazineinduced EPS in schizophrenic patients. Methods: We identified seven SNP(single nucleotide polymorphism) TaqIB, TaqID, Ser311Cys, rs6275, rs6277 and TaqIA) in the DRD2 gene in 146 schizophrenic inpatients (59 with EPS and 87 without EPS according to the Simpson-Angus Scale) treated with chlorpromazine after 8 weeks. The alleles of all loci were determined by PCR (polymerase chain reaction) . Results: Polymorphisms TaqID, Ser311Cys and rs6277 were not polymorphic in the population recruited in the present study. No statistical significance was found in the allele distribution of -141Cins>del, TaqIB, rs6275 and TaqIA or in the estimated haplotypes (constituted by TaqIB, rs6275 and TaqIA) in linkage disequilibrium between the two groups. Conclusion: Our results did not lend strong support to the view that the genetic variation of the DRD2 gene plays a major role in the individually variable adverse effect induced by chlorpromazine, at least in Chinese patients with schizophrenia. Our results confirmed a previous study on the relationship between DRD2 and EPS in Caucasians.

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Cebus apella, a nonhuman primate highly susceptible to neuroleptic side effects, carries the GLY9 dopamine receptor D3 associated with tardive dyskinesia in humans

Cited by 17 publications

References 23 publications

Combined analysis of 635 patients confirms an age-related association of the serotonin 2A receptor gene with tardive dyskinesia and specificity for the non-orofacial subtype

Combined analysis of 635 patients confirms an age-related association of the serotonin 2A receptor gene with tardive dyskinesia and specificity for the non-orofacial subtype

Nonhuman Primate Research Contributions to Understanding Genetic and Environmental Influences on Phenotypic Outcomes across Development

Association of DRD2 polymorphisms and chlorpromazine-induced extrapyramidal syndrome in Chinese schizophrenic patients1

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