CYP2D6 HhaI genotype and the neuroleptic malignant syndrome

To investigate the relationship between CYP2D6 genotypes (reported to be associated with the susceptibilities to Parkinson's disease and multisystem atrophy) and the possible susceptibility to neuroleptic malignant syndrome (NMS) and subacute myelo-optico-neuropathy (SMON), we analyzed the CYP2D6 gene by polymerase chain reaction and restriction fragment length polymorphism in Japanese schizophrenia patients with a history of NMS. There was no significant difference in the frequency of the poor metabolizer genotype of CYP2D6 between the cases with a history of NMS and controls (p > 0.05). The frequency of the mutation located at the HhaI site in exon 6 of CYP2D6 in the cases was higher, but not significantly (p > 0.05; the mutated allele frequency was 0.25), than that in the controls, schizophrenia patients without NMS (0.11) and healthy controls (0.09). The frequency (0.10) of the HhaI mutation type in patients with a diagnosis of SMON was also not significantly higher than in healthy controls. These results suggest that the poor metabolizer and HhaI polymorphism of CYP2D6 may not be a useful molecular marker for predicting the onset of NMS and SMON.