Although met with conflicting data, the following genes may be involved with TD development: the cytochrome P450 gene CYP2D6, involved with metabolism of most antipsychotics, Dopamine D2 and D3 receptor genes, serotonin 2A and 2C receptor genes, vesicular monoamine transporter 2 (VMAT 2) gene, involved with intracellular neurotransmitter packaging, and the manganese superoxide dismutase (MnSOD) gene, an antioxidant enzyme.
In patients tested for CYP2D6, an association between genotype and tardive dyskinesia (including Abnormal Involuntary Movement Scale scores) was found.
This study tested the association between tardive dyskinesia (TD) and polymorphic variations in (a) 2 cytochrome P450 (CYP) genes (CYP2D6 or CYP3A5), (b) 2 DRD2 variants (Ser311Cys and -141C Ins/del) and the Ser9Gly DRD3 variants, (c) 2 glutathione S-transferases (GSTT1 and GSTM1), and (d) variations in the PgP gene, MDR1.
We concluded that the CYP2D6*10 C188T polymorphism may be associated with the susceptibility to the occurrence of TD induced by typical antipsychotics, especially in male patients, and may also be correlated with AIMS scores in TD patients.
However, no significant difference was observed in the distribution of both CYP2D6*2 (C2938T) and CYP2D6*10 (C188T) polymorphisms between schizophrenic patients with or without tardive dyskinesia.
The tendencies for patients carrying at least one mutated CYP2D6 gene to have an increased risk of parkinsonism and TD are in accordance with previous studies.
The goal of this study was to determine whether the occurrence of TD is associated with CYP2D6 genotype in a cohort of Korean schizophrenics by employing a CYP450 GeneChip((R)) oligonucleotide microarray and PCR assays to screen for 19 CYP2D6 alleles.
As slight differences in the metabolism of drugs in patients heterozygous for CYP2D6 mutations and patients without such mutations are known, we conclude that heterozygous carriers of 2D6 mutated alleles may show an increased susceptibility to developing TD.
CYP2D6 genotype is not a determinant of susceptibility to acute dystonic reactions but may be a contributory factor in antipsychotic drug-induced movement disorders including tardive dyskinesia.
Sixteen white schizophrenic patients who had developed tardive dyskinesia during long-term neuroleptic treatment were phenotyped with debrisoquine and genotyped by CYP2D6-specific DNA amplification and EcoRI restriction fragment length polymorphism analysis.