Relationship between functional dopamine D2 and D3 receptors gene polymorphisms and neuroleptic malignant syndrome.
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 Ser(9)Gly 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 Ser(9)Gly polymorphisms are not.
Mihara
Kazuo
K
Department of Neuropsychiatry, Hirosaki University School of Medicine, Hirosaki, Japan.
Kondo
Tsuyoshi
T
Suzuki
Akihito
A
Yasui-Furukori
Norio
N
Ono
Shingo
S
Sano
Akira
A
Koshiro
Kazuko
K
Otani
Koichi
K
Kaneko
Sunao
S
D000328:Adult; D015252:Deoxyribonucleases, Type II Site-Specific; D003863:Depression / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009459:Neuroleptic Malignant Syndrome / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000502:physiology*; D017448:Receptors, Dopamine D2 / Q000235:genetics*; D050637:Receptors, Dopamine D3; D012559:Schizophrenia / Q000235:genetics
C493593:DRD3 protein, human; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; D015252:Deoxyribonucleases, Type II Site-Specific; C027046:TCGA-specific type II deoxyribonucleases