THE STUDY OF THE POLYMORPHIC VARIANT OF THE DOPAMINE-BETA-HYDROXYLASE RS1611115 (C-1021T) GENE WITH THE CONTENT OF FREE FATTY ACIDS IN THE BLOOD SERUM OF SCHIZOPHRENIC PATIENTS TREATED WITH HALOPERIDOL AND RISPERIDONE (RESULTS OF AN ORIGINAL RESEARCH)

Abstract

Relevance. According to various authors, the metabolic syndrome is common in more than 50 % of patients with schizophrenia. One of the reasons for the formation of the metabolic syndrome is the excessive content of non5esterified fatty acids (NEFA) in the blood. It is known that antipsychotic therapy in patients with schizophrenia is associated with an increase in the amount of NEFA in the blood serum. Dopamine5beta5hydroxylase (DβH) is an enzyme involved in the metabolism of dopamine and norepinephrine. Some polymorphic variants of the DβH gene are associated with metabolic disorders such as obesity and type 2 diabetes. Research objective - to study the association between the polymorphic variant of the dopamine5β5hydroxylase (DβH) rs1611115 gene and the content of non5 esterified fatty acids in patients with the first episode of paranoid schizophrenia treated with haloperidol and risperidone. Material and methods. The study included 212 patients (109 male and 103 female patients) with a diagnosis of «paranoid Schizophrenia, follow5up period less than a year» (F20.09). The age of the patients was 27 ± 6 years. The control group included 132 healthy volunteers. The patients and representatives of the control group were of Caucasian race, were born and lived in the territory of the Trans5Baikal Territory. They were comparable in gender and age. Human genomic DNA was isolated from whole blood white blood cells. The analysis of rs1611115 was carried out by polymerase chain reaction with electrophoretic detection of products. The content of NEFA in the blood serum was measured using the colorimetric method for determining copper salts. The level of glycerol in the blood serum was determined by an enzymatic photometric test with glycerol535phosphate oxidase. The coefficient of «NEFA/glycerol», reflecting the degree of utilization of fatty acids, was calculated. Results. In patients with the first episode of paranoid schizophrenia, an increased content of NEFA in the blood serum was established even before the start of antipsychotic therapy. At the same time, there were no differences in the amount of NEFA and free serum glycerol between carriers of the C/C and C/T + T/T genotypes. Therapy with haloperidol and risperidone was accompanied by an increase in the concentration of NEFA in the blood serum. In patients treated with risperidone, at the 8th week of the study, the content of NEFA in the blood serum did not differ between carriers of the C/C and C/T + T/T genotypes, while, in the group of patients taking haloperidol, at the 8th week of therapy, the concentration of NEFA in the serum of carriers of the C/C genotype was greater than in carriers of the C/T + T/T genotypes. Different effects of haloperidol and risperidone on the content of NEFA and free glycerol in blood serum were found only in carriers of the C/C genotype. Conclusion. Therapy with haloperidol and risperidone in patients with the first episode of schizophrenia is accompanied by an increase in the content of NEFA in the blood serum. The severity of these changes depends not only on the neuroleptic used, but also on the carrier of the rs1611115 genotypes. Further pharmacogenetic studies are needed to study the metabolic effects of antipsychotics depending on the genetic characteristics of patients in order to develop a personalized approach to therapy.