Associative studies of polymorphic variants of adrenergic receptor genes and tardive dyskinesia in schizophrenia

The adrenergic system, along with the dopaminergic, serotonergic and glutamatergic systems, plays an important role in the pathophysiology of schizophrenia and response to the applied pharmacotherapy. Tardive or late dyskinesia (TD) is a serious side effect and can develop in schizophrenic patients with prolonged use of antipsychotics. An important role in the pathogenesis of TD belongs to genetic factors. The aim of this study was to search for possible associations of polymorphic variants of the ADRβ1 and ADRA1A genes with the development of tardive dyskinesia in schizophrenic patients receiving antipsychotic therapy. We examined 449 patients from Russian population of Siberian region with verified diagnosis of schizophrenia. 121 patients from whole group met the criteria for tardive dyskinesia. Genotyping of the polymorphic variants rs1801253, rs2036108, rs472865 of the ADRβ1 and ADRA1A genes was performed by real-time PCR using a QuantStudio 5 amplifier using TaqMan kits. The associative analysis of the frequencies of genotypes and alleles was assessed using the χ2 test in the R 3.6.2 program using basic functions and an additional SNPassoc package. The distribution of genotype and allele frequencies for the rs2036108 polymorphic variant of the ADRA1A gene significantly differs in the groups of patients with tardive dyskinesia and without side effects (for genotypes p = 0.028; for alleles p = 0.040). For the first time, the association of the rs2036108 polymorphic variant of the ADRA1A gene with tardive dyskinesia in schizophrenic patients was revealed. Further studies of the role of adrenergic receptor genes in the development of tardive dyskinesia are required to develop pharmacogenetic approaches to personalizing therapy.

schizophrenia, polymorphism, adrenergic receptors, tardive dyskinesia

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