Polymorphic variants of the ANKS1B rs7968606 (C>T) and ZNF804A rs1344706 (G>T) genes are not associated with the efficacy and safety of antipsychotics in adolescents with an acute psychotic episode

Background. The pharmacogenetics of antipsychotics in adolescents is currently not well understood. Polymorphic variants of the ANKS1B rs7968606 and ZNF804A rs1344706 genes have demonstrated their significance in studies on adults who received antipsychotics for the treatment of schizophrenia. Objective. Evaluation of the predictive role of the ANKS1B rs7968606 and ZNF804A rs1344706 gene polymorphisms for the efficacy and safety of antipsychotics in adolescents with an acute psychotic episode. Methods. The study included 101 adolescents with an established diagnosis of acute polymorphic psychotic disorder at admission (F23.0-9 according to ICD-10). All patients received an antipsychotic medication as their primary therapy. The patients were followed up for 14 days. The effectiveness of antipsychotics was assessed using the CGAS (Children’s Global Assessment Scale), PANSS (Positive and Negative Symptoms Scale), CGI-S (Clinical Global Impression Severity) and CGI-I (Improvement); the safety of pharmacotherapy - according to the UKU SERS (UKU Side Effects Rating Scale), SAS (Sympson-Angus Scale), BARS (Barnes Akathisia rating scale). A scraping of the buccal epithelium was obtained from each patient, from which DNA was extracted by the sorbent method, and the carriage of polymorphic variants of the ANKS1B rs7968606 (G> T) and ZNF804A rs1344706 (A> C) genes was detected by real-time polymerase chain reaction. Statistical analysis was carried out using the SPSS Statistics 21.0 software. Given the small sample size, nonparametric tests (Mann - Whitney, Kruskal - Wallis) were used to compare quantitative variables between groups. Results. No significant associations of efficacy and safety parameters of pharmacotherapy depending on the carriage of the ANKS1B rs7968606 and ZNF804A rs1344706 polymorphic variants were found. It was revealed that carriers of the «wild» genotype AA ZNF804A rs1344706 polymorphic variant were more likely to receive a normotimic agent compared to carriers of AC+CC (33.3% versus 9.7%, respectively; p=0.004). Also, carriers of the T ANKS1B rs7968606 polymorphic allele were characterized by a higher degree of severity of psychotic symptoms at the time of inclusion in accordance with the total PANSS score, as well as its “General Symptoms" subscale score (p=0.003). Conclusion. As a result of the study, no significant associations were found between the parameters of the efficacy and safety of pharmacotherapy and the carriage of ANKS1B rs7968606 (G>T) and ZNF804A rs1344706 (A>C) gene polymorphisms in adolescents with an acute psychotic episode.

ZNF804A, pharmacogenetics, antipsychotics, ANKS1B genes, ZNF804A, acute psychotic episode