The role of dopamine D3, 5-HT2A and 5-HT2C receptor variants as pharmacogenetic determinants in tardive dyskinesia in African-Caribbean patients under chronic antipsychotic treatment: Curacao extrapyramidal syndromes study IX.
Tardive dyskinesia (TD) is associated with polymorphisms of the dopamine D(3), serotonin 2A and 2C receptors (DRD3, HTR2A and HTR2C, respectively). This study investigated the possible relationship between TD and the polymorphisms Ser9Gly (DRD3), 102T>C (HTR2A), -1438G>A(HTR2A) and Cys23Ser (HTR2C) in African-Caribbean inpatients. One hundred and twenty-six patients under chronic antipsychotic treatment were genotyped. The assessment of TD was carried out with the abnormal involuntary movement scale (AIMS). The relationships between the carriership of the least frequent alleles and the respective orofaciolingual dyskinesia (TDof) (sum of the items 1-4 of the AIMS), limb-truncal dyskinesia (TDlt) (sum of items 5-7 of the AIMS) and TD (sum of items 1-7 of the AIMS) were analyzed with ANCOVA, comparing means with age as a covariate and stratification for carriers and non-carriers of the mutations. In addition, we conducted pre-planned t-tests to compare AIMS values of carriers of the combinations of alleles versus the corresponding non-carriers. In the study population, females with 9Ser carriership exhibited higher AIMS values than non-carriers. Male subjects with 9Ser carriership in combination with 23Ser or -1438A carriership exhibited higher AIMS values. In male patients also, the combination of 23Ser and -1438A carriership increased TD. The study clearly shows that the African-Caribbean population differs from the Caucasian population with regard to the association of TD with the polymorphisms studied and suggests that the association of TD with the studied polymorphisms of the 5-HT(2C) and probably of the 5-HT(2A) receptor are the result of a changed susceptibility of the patients, independent of the action of the antipsychotics on these receptors.
Department of Pharmacotherapy and Pharmaceutical Care, University of Groningen, Groningen, The Netherlands. B.Wilffert@ZNB.NL
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Wilffert
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Al Hadithy
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Sing
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Matroos
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Hoek
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van Os
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Bruggeman
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Brouwers
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van Harten
D000328:Adult; D000368:Aged; D000375:Aging / Q000502:physiology; D000483:Alleles; D014150:Antipsychotic Agents / Q000009:adverse effects*; D044383:Black People; D004247:DNA / Q000235:genetics; D004409:Dyskinesia, Drug-Induced / Q000235:genetics* / Q000523:psychology*; D005260:Female; D005787:Gene Frequency; D014644:Genetic Variation; D005838:Genotype; D006579:Heterozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D009427:Netherlands Antilles / Q000453:epidemiology; D044402:Receptor, Serotonin, 5-HT2A / Q000187:drug effects* / Q000235:genetics*; D044405:Receptor, Serotonin, 5-HT2C / Q000187:drug effects* / Q000235:genetics*; D050637:Receptors, Dopamine D3 / Q000187:drug effects* / Q000235:genetics*
D014150:Antipsychotic Agents; D044402:Receptor, Serotonin, 5-HT2A; D044405:Receptor, Serotonin, 5-HT2C; D050637:Receptors, Dopamine D3; D004247:DNA