Abstract
Clozapine was the first antipsychotic agent which did not induce extrapyramidal symptoms. This medicament was withdrawn from the market because of its myelotoxicity, but came back several years later due to its treatment effects on pharmacoresistant schizophrenia.
Pharmacogenetics concerns associations between the genetic background of a concrete patient with a given medicament's effects. From the pharmacogenetic point of view, clozapine probably was the most studied antipsychotic drug.
Pharmacogenetics of clozapine was comprehensively reviewed by Arranz et al. in 2011. As of the treatment efficacy, the genes related to serotonin and dopamine are promising.
Agranulocytosis induced by clozapine was definitely associated with the polymorphisms of HLA genes. Zhang and Malhotra suggested further development in the research of clozapine's pharmacogenetics in 2013.
It seems to be more favourable to study adverse side effects (body weight increase, myelotoxicity) than the treatment efficacy, because etiology of adverse side effects is more simple than a complex therapeutic effect of a medicament. Epigenetic knowledge related to clozapine is only emerging.
According to Dong et al., hypermethylation of promoters of the GAD67 and reelin genes is present in schizophrenia, resulting in a GABA hypofunction. This DNA hypermethylation may be eliminated by clozapine.