Antipsychotic-induced hyperprolactinemia: pharmacogenetic aspects

The pathogenesis of the development of drug-induced disorders against the background of taking antipsychotic drugs was not studied enough. The aim of the work was to study polymorphic variants of pharmacodynamic and pharmacokinetic genes in antipsychotic-induced hyperprolactinemia in patients with schizophrenia. A comprehensive clinical and molecular genetic study was conducted in 446 patients with schizophrenia receiving antipsychotic treatment. Genotyping was carried out on polymorphic variants of genes HTR2C, HTR3A, HTR3B, HTR6, HTR2A, HTR1A, HTR1B, DRD1, DRD2, DRD2/ANKK1, DRD3, DRD4, CYP1A2*1F, CYP2D6*3, CYP2D6*4, CYP2D6*6, CYP2C19*3, CYP2C19*17, CYP2C19*2, GSTP1. The associations were revealed of polymorphisms of the genes of serotonin receptors HTR2A (rs6312) and HTR2C (rs12858300, rs569959) with the development of hyperprolactinemia. Based on the results of genotyping and analysis of clinical data a pharmacogenetic panel was developed that could be used as biological predictors of the development of antipsychotic-induced hyperprolactinemia in schizophrenia. The results of the research showed that the polymorphic characteristics of the genes of neurotransmitter receptors and the cytochrome system are an important link in the pathogenesis of side effects observed against the background of antipsychotic treatment in patients with schizophrenia. Perspective directions of further research are the studies of genes that hypothetically involved in the mechanisms of the onset of hyperprolactinemia: drug transporters, genes of antioxidant enzymes and genes of neurotrophic factors.