Potential association of CYPs, COMT, DRD2, 5HTR2A polymorphisms with susceptibility to the adverse effect of aripiprazole: preliminary observations

Introduction: Aripiprazole is a third-generation antipsychotic drug generally well tolerated, but some patients experience adverse effects. Variability in a patient’s response to aripiprazole can be associated with genetic variants in genes involved in drug pharmacokinetics and pharmacodynamics. The purpose of this study was to perform genetic profiling on patients with schizophrenia, bipolar disorder, and personality disorder to find an association between SNPs and adverse events. Materials and methods: The gDNA of 74 patients was used to assess 71 polymorphisms in 21 genes by mass spectrometric analysis and PCR-RFLP method. Results: Patients were divided into well- and badly-reacting groups. The CYP2D6 UM/NM phenotypes and the combined homozygous genotype CYP1A2*1F/CYP2B6*1 were observed more frequently in the badly-reacting group. Moreover, the frequency of the combined homozygous status of 5HTR2A (AA/TT rs6311/rs6313) differed significantly between groups. For the polymorphism of the COMT rs4680 variant, the frequency of the A allele was significantly higher in the well-reacting group. Conclusions: The present preliminary findings showed that polymorphisms of the DRD2 and 5HTR2A genes may be related to adverse drug effects. Alleles determining the higher density of receptors were observed more frequently in the badly reacting group. Moreover, the G allele of COMT was observed significantly more frequently in patients who experienced adverse effects. Surprisingly, it was noticed that patients in the badly reacting group most often had the CYP2D6 UM/NM phenotype, which does not require standard dose adjustments.