Absence of Effect of Single Nucleotide Variants of ABCB1 and ABCG2 Genes On QTс Interval Prolongation during Clozapine Therapy

Background: clozapine remains the drug of choice for treatment of resistant schizophrenia; however, its use is limited by the high risk of adverse drug reactions, including prolongation of the QTc interval. The role of genetic factors, in particular polymorphisms of the genes of transport proteins, in the development of this complication has not been sufficiently studied.

The aim of the study was to evaluate the association between low-function single nucleotide variants (SNVs) of the ABCB1 (rs1045642, rs1128503, rs2032582) and ABCG2 (rs2231142) genes and prolongation of the QTc interval in patients with schizophrenia taking clozapine.

Patients and Methods: the study included 129 patients with paranoid schizophrenia (F20.0 on ICD-10) receiving clozapine. Correction of the QTc interval was performed according to the Frederick formula. QTc interval prolongation was defined as an increase of ≥ 30 ms from baseline. Genotyping was performed using real-time PCR.

Results: an increased risk of QTc interval prolongation was found in women (OR 4.217; 95% CI: 1.556–11.430; p = 0.003) and older people (ρ(rho) 0.218; p = 0.02). Antipsychotic polytherapy was not associated with an increased risk of QTc interval prolongation (p = 0.097). No statistically significant association was found between single nucleotide variants of the ABCB1 (rs1045642, rs1128503, rs2032582), ABCG2 (rs2231142) genes and QTc prolongation (p > 0.05).

Discussion: foreign studies have shown a high risk of prolongation of the QTc interval when taking clozapine. In this regard, further study and clarification of the pharmacogenetics of clozapine and the search for predictors of prolongation of the QTc interval when taking it are required.

Conclusion: prolongation of the QTc interval is associated with female gender and older age. The studied single nucleotide variants of the genes of transport proteins do not have a significant effect on prolongation of the QTc interval during clozapine therapy. Regular electrocardiographic monitoring is recommended in patients at risk of prolongation of the QTc interval.

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