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Background: Metabolic syndrome (MetS) occupies an important place among the main problems of the somatic state of schizophrenia patients. MetS is characterized by abdominal obesity, hyperglycemia, dyslipidaemia and hypertension. Certain role belongs to genetic factors that might be the basis of sensitivity to development of metabolic syndrome. FTO gene has been implicated in the pathogenesis of obesity, but the available scientific data concerning their relationship to antipsychotic drug-induced obesity and metabolic syndrome is still incomplete and inconsistent, which indicates that continuing the investigation of this gene's role is necessary. Methods: The aim is to determine 6 polymorphisms of FTO gene in schizophrenia patients with metabolic syndrome and to study associations with body mass index. After obtaining informed consent, 517 patients with schizophrenia receiving long-term antipsychotic treatment were included. Patients were divided into two groups: 139 (26.9%) with MetS and 378 (73.1%) without it. Clinical verification of metabolic syndrome was carried out using the criteria of the International Diabetes Federation (IDF, 2000). A blood sample was obtained for DNA isolation and genotyping. All genotyping was performed without knowledge of the patient's clinical status. Determination of 6 polymorphisms of FTO gene (rs7185735, rs9939609, rs1421085, rs1861868, rs3751812, rs8050136) was performed on SEQUENOM MassARRAY® Analyzer 4 (The Core Facility "Medical Genomics", Tomsk NRMC). The calculations were carried out in the specific statistical software SPSS and with the use the scripting programming language R 3.6.1 in the RStudio 1.2.5001 environment. Frequency distribution of the study sample was tested in accordance to Hardy-Weinberg equilibrium. The critical significance level was 0.05. Results: We performed a statistical analysis to identify possible associations of the frequencies of genotypes and alleles of the studied polymorphisms with the presence of metabolic syndrome in schizophrenic patients and with an increased body mass index (BMI). The rs7185735 polymorphism did not meet the Hardy-Weinberg criterion and was excluded. After correcting for differences in age, gender and duration of illnesses none of the variants was shown to be related to metabolic syndrome, but rs9939609, rs1421085, rs3751812 and rs8050136 were associated with body mass index. Increased BMI is associated with the carriage of certain genotypes and alleles of polymorphisms in the FTO gene: rs9939609 (χ2=7.989, p=0.018), rs1421085 (χ2=6.859, p=0.032), rs3751812 (χ2=7.638, p=0.022), rs8050136 (χ2=8.298, p=0.016). Discussion: The FTO gene is known to be important for metabolic syndrome and has previously been associated with number of different diseases and clinical phenotypes. We found no relationship with metabolic syndrome itself. A relationship with BMI existed however and therefore presumably also with antipsychotic drug induced body weight gain. This was more specifically true for rs9939609, rs1421085, rs3751812, and rs8050136 polymorphisms, which were also significantly related after correcting for difference in age, gender and duration of disorder. |
