Analysis of associations of G1444A polymorphisms of PPARGC1A gene and A1166C polymorphisms of AGTR1 gene with premorbid personality schizophrenia

Background: it is assumed that a number of metabolic changes and initial psychopathological anomalies of patients with endogenous psychoses are formed long before the manifestation of the disease, is associated with a hereditary, genetic component and can be reflected in the constitutional features of the patients already in the premorbid period of the disease and be a promising method for early recognition. Previously, the participation of PPARGC1A (Peroxisome proliferator-activated receptor gamma coactivator 1-alpha) and AGTR1(Angiotensin II Receptor Type 1) genes in the formation of both metabolic and morphofunctional, neurodegenerative, cognitive and other mental disorders was repeatedly demonstrated. The aim of study was to study the frequency distribution of the polymorphic markers G1444A of the PPARGC1A gene (rs8192678) and A1166C of the AGTR1 gene (rs5186) in patients with schizophrenia (ICD-10: F20, F25), depending on their afliation to the subgroups isolated according to the severity of premorbid personality anomalies: accentuated, with personality disorder (or psychopathy), with pseudopsychopathy. Material: a sample of patients was formed of in-patients (all men) of clinical unit of FSBSI «Mental health research centre». The control group consisted of 290 healthy men. DNA for the study was isolated from the venous blood of the recipients. Methods: genotyping was performed by standard PCR with further analysis of MspI restriction fragments (for rs8192678) and DstDEI fragments (for rs5186). Statistical processing of data was carried out using the program Statistica 6.0. Results: the association of studied markers with the severity of premorbid personality anomalies in patients was revealed. Thus, in the subgroup of patients with personality disorder, an increase in the frequency of the CC genotype (A1166C of the AGTR1 gene) and a decrease in the frequency of the GG genotype (G1444A of the PPARGC1A gene) compared to other subgroups; and in the subgroup of patients with pseudopsychopathy — a decrease in the frequency of the genotype CC (A1166C gene AGTR1) and an increase in the frequency of the genotype GG (G1444A gene PPARGS1A). This may indicate the possible involvement of these genes in the formation of psychopathological and biological changes in patients with schizophrenia at the stages preceding the manifestation of the disease.

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