RESUMO
Recent studies demonstrate an association between antipsychotic-induced parkinsonism (AIP) and rs4606 SNP of RGS2 gene in Jewish and African-Americans. The current study investigates the association between rs4606 and AIP or its subsymptoms (rest tremor, rigidity, and bradykinesia) in 112 psychiatric inpatients of African-Caribbean origin. Presence of AIP, rigidity, bradykinesia, and tremor was measured by the UPDRS. We applied chi(2) (or Fisher Exact) and logistic regression analyses in several models including rs4606, age, gender, dose of antipsychotics, and anticholinergics, and two other putatively functional SNPs in DRD2 (-141CIns/Del) and HTR2C (Cys23Ser) genes. In contrast to recent literature, we find no evidence for an association between rs4606 and AIP or any of its subsymptoms. We hypothesize that the observed lack of association is due probably to differences in serotonin 2A-receptor affinities of the antipsychotics utilized (in contrast to the other published studies, the majority of our patients utilized typical antipsychotics).
Assuntos
Antipsicóticos/efeitos adversos , Transtornos Parkinsonianos/genética , Polimorfismo de Nucleotídeo Único , Proteínas RGS/genética , Adulto , Fatores Etários , Antipsicóticos/administração & dosagem , Antipsicóticos/farmacologia , População Negra , Relação Dose-Resposta a Droga , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Transtornos Parkinsonianos/induzido quimicamente , Escalas de Graduação Psiquiátrica , Receptor 5-HT2A de Serotonina/metabolismo , Fatores de Risco , Fatores Sexuais , Índias OcidentaisRESUMO
We studied the association between polymorphisms of genes coding for dopamine D(2) (DRD2), dopamine D(3) (DRD3), serotonin 2(a) (HTR2A), and serotonin 2(c) (HTR2C) receptors and Antipsychotic-Induced Parkinsonism (AIP), rigidity, bradykinesia, and rest-tremor in African-Caribbeans treated with antipsychotics. Polymorphisms of DRD2 (-141CIns/Del, TaqIA, 957C > T), DRD3 (Ser9Gly), HTR2A (-1438A > G, 102T > C, His452Tyr), and HTR2C (-759C > T, Cys23Ser) genes were determined according to standard protocols. The Unified Parkinson Disease Rating Scale was used for the measurement of AIP, rigidity, bradykinesia, and rest-tremor. Chi-squared or Fisher's exact tests were applied for the association analyses. The t-test was applied for continuous data. Ninety nine males and 27 females met the inclusion criteria (Schizophr Res 1996, 19:195). In males, but not in females, there were significant associations between -141CDel-allele carriership (DRD2) and rigidity (Fisher's Exact Test: P = 0.021) and between 23Ser-allele carriership (HTR2C) and bradykinesia (P = 0.026, chi(2) = 5.0) or AIP (P = 0.008, chi(2) = 7.1). Rest-tremor was not associated with any of the polymorphisms studied. Analyses of the age, chlorpromazine equivalents, benztropine equivalents, the number of patients using anticholinergic medication, and the utilization patterns of the antipsychotic medication did not show statistically significant differences between patients with and without AIP, rigidity, bradykinesia, rest-tremor. Conducting the analysis without gender stratification did not affect our findings considerably, except for the association between bradykinesia and 23Ser-allele which failed to reach statistical significance in the total sample (P = 0.0646, chi(2) = 3.41). Since AIPs subsymptoms (rigidity, bradykinesia, and rest-tremor) may differ pharmacogenetically, our data strongly support symptom-specific analysis of AIP. However, further research is warranted to confirm our findings.