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.


METHODS
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.
Suzuki
A
A
Department of Neuropsychiatry, Hirosaki University School of Medicine, Hirosaki 036-8562, Japan.
Kondo
T
T
Otani
K
K
Mihara
K
K
Yasui-Furukori
N
N
Sano
A
A
Koshiro
K
K
Kaneko
S
S
D000328:Adult; D014150:Antipsychotic Agents / Q000009:adverse effects / Q000627:therapeutic use; D003866:Depressive Disorder / Q000188:drug therapy / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D009459:Neuroleptic Malignant Syndrome / Q000209:etiology / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic / Q000235:genetics*; D012150:Polymorphism, Restriction Fragment Length; D017448:Receptors, Dopamine D2 / Q000235:genetics*; D012559:Schizophrenia / Q000188:drug therapy / Q000235:genetics; D019914:Taq Polymerase / Q000235:genetics*
D014150:Antipsychotic Agents; D017448:Receptors, Dopamine D2; D019914:Taq Polymerase