Association of the TaqI A polymorphism of the dopamine D(2) receptor gene with predisposition to neuroleptic malignant syndrome.

OBJECTIVE The pathophysiology of neuroleptic malignant syndrome is mainly explained by a central hypodopaminergic state. The familial occurrence of neuroleptic malignant syndrome suggests the involvement of a genetic mechanism in the predisposition to the syndrome. Therefore, the authors examined the association between the TaqI A polymorphism of the dopamine D(2) receptor gene (DRD(2)), which alters DRD(2) density and function, and the development of neuroleptic malignant syndrome. METHOD The subjects were 15 psychiatric patients who had developed neuroleptic malignant syndrome (12 patients with schizophrenia and three with major depression) and 138 patients with schizophrenia who had never developed neuroleptic malignant syndrome. The TaqI A genotypes, A1 and A2 alleles, were determined by the polymerase chain reaction method. RESULTS The frequency of the A1 allele was significantly higher in the patients who had developed neuroleptic malignant syndrome (56.8%) than in the patients who had not (35.1%). The proportion of the A1 carrier was significantly higher in the patients with neuroleptic malignant syndrome (14 [93.3%] of 15 patients) than in those without the syndrome (79 [57.2%] of 138 patients). CONCLUSIONS These findings suggest that the TaqI A DRD(2) polymorphism is associated with the predisposition to neuroleptic malignant syndrome.