Relationship between functional dopamine D2 and D3 receptors gene polymorphisms and neuroleptic malignant syndrome

Abstract

Our previous study has suggested that the TaqI A polymorphism of dopamine D2 receptor gene (DRD2) is associated with the predisposition to neuroleptic malignant syndrome (NMS). However, the specificity of this polymorphism as a predictor of NMS dose not seem to be sufficient enough. Meanwhile, it has been shown that the non‐carriers of Del allele of the −141C Ins/Del polymorphism in the promoter region of DRD2 have lower dopamine D2 receptor in the brain than the carriers. In addition, dopamine D3 receptor gene has a Ser₉Gly polymorphism, which may alter the receptor function. The present study examined the association between these three polymorphisms and the development of NMS to investigate if a combination of these polymorphisms could increase the specificity as markers for NMS. The subjects were 17 psychiatric patients who had developed NMS (13 patients with schizophrenia, 3 with major depression, and 1 with dementia of the Alzheimer's type) and 163 schizophrenic patients who had never developed this syndrome. The frequency of the A1 allele was significantly (P = 0.012) higher in the patients who had developed NMS (59%) than in the patients who had not (35%). The proportion of the A1 carriers was significantly (P = 0.003) higher in the patients with NMS (16/17: 94%) than in those without the syndrome (93/163: 57%). However, no significant differences were found in the allele and genotype frequencies of the other two polymorphisms between the two groups. The present study suggests that only the TaqI A polymorphism is at least partly useful as a predictor of NMS, but the −141 C Ins/Del and Ser₉Gly polymorphisms are not.