RESUMEN
A genetic predisposition to the development of neuroleptic malignant syndrome (NMS) has been suggested by clinical studies. Although the molecular basis of NMS is unclear, a dopaminergic blockade mechanism has been considered the main cause. We therefore investigated the association between NMS and three functional polymorphisms of the dopamine D(2) receptor (DRD(2)) gene: TaqI A, -141C Ins/Del, and Ser311Cys. Subjects included 32 Japanese patients, previously diagnosed with NMS, and 132 schizophrenic patients treated with neuroleptics without occurrence of NMS. Polymerase chain reaction and restriction fragment length polymorphism analyses were performed to determine each genotype. We found significant differences in genotypic and allelic frequencies of the -141C Ins/Del polymorphism between patients with and without NMS. The -141C Del allele was significantly more frequent in the NMS group (23.4 vs 11.7%, P=0.026). Similarly, the proportion of -141C Del allele carriers was significantly higher in the NMS group (40.6 vs 20.5%, P=0.022). No significant differences between the two groups were seen for allelic and genotypic frequencies of the TaqI A and Ser311Cys polymorphisms. This result suggests that the -141C Ins/Del polymorphism is likely to predispose toward the development of NMS, probably together with other unidentified factors.
Asunto(s)
Síndrome Neuroléptico Maligno/genética , Polimorfismo Genético/genética , Receptores de Dopamina D2/genética , Sustitución de Aminoácidos , Pueblo Asiatico/genética , Intervalos de Confianza , ADN/sangre , ADN/aislamiento & purificación , Femenino , Frecuencia de los Genes , Tamización de Portadores Genéticos , Genotipo , Humanos , Japón , Leucocitos , Masculino , Persona de Mediana Edad , Oportunidad Relativa , Reacción en Cadena de la Polimerasa , Polimorfismo de Longitud del Fragmento de Restricción , Eliminación de SecuenciaAsunto(s)
Inhibidores de la Colinesterasa/efectos adversos , Indanos/efectos adversos , Síndrome Neuroléptico Maligno/psicología , Piperidinas/efectos adversos , Anciano , Inhibidores de la Colinesterasa/uso terapéutico , Donepezilo , Femenino , Humanos , Indanos/uso terapéutico , Enfermedad por Cuerpos de Lewy/complicaciones , Enfermedad por Cuerpos de Lewy/tratamiento farmacológico , Piperidinas/uso terapéuticoRESUMEN
We describe a patient with treatment-resistant schizophrenia who had a duplication in the cytochrome P450IID6 (CYP2D6) gene. This severely ill 71-year-old-woman had responded poorly to several neuroleptics. Molecular genetic study revealed CYP2D6 gene duplication, which results in excessive activity of CYP2D6 that metabolizes various commonly used neuroleptics. The mutation may have contributed to treatment resistance in this case.
