THE PREVALENCE OF C3953T IL1Β GENE AND G308A TNFΑ GENE POLYMORPHIC VARIANTS IN THE PATIENTS WITH DIFFERENT TYPES OF ENCEPHALOPATHIES.

It is essential to study disorders of the immune system in chronic encephalopathies of various genesis, considering that the mechanisms of brain damage remain unknown in their molecular basis. Among numerous inflammatory mediators, cytokines are particular in regulating immunological interactions. Many factors, including the genetic ones, determine these pro-inflammatory proteins' activity. The aim of study was to study the prevalence of IL1β C3953T gene polymorphism and TNFα G308A gene polymorphism in patients with chronic traumatic encephalopathy (CTE), microvascular ischemic disease of the brain (or cerebral small vessel disease, (SVD)), chronic alcohol-induced encephalopathy (AIE) and postinfectious encephalopathy (PIE), and to evaluate the impact of a particular genotype presence on the occurrence and/or progression of encephalopathy. The molecular genetic study of polymorphic variants - C3953T of the IL1β gene and G308A of the TNFα gene was applied for 96 patients with encephalopathies of various genesis (CTE n=26, CAIE n=26, SVD n=18, and PIE n=26). The patients were undergoing treatment in the neurological departments of the Communal Non-commercial Enterprise "Ternopil Regional Clinical Psychoneurological Hospital" of Ternopil Regional Council (Ternopil, Ukraine) during 2021-2022. The control group consisted of 12 healthy persons, who were representative in terms of age and sex. Statistical processing of the results was carried out using the STATISTICA 10.0 software package. The frequency distribution analysis of the genotypes of the polymorphic variant C3953T of the IL1β gene and G308A of the TNFα gene in patients with CTE, SVD, CAIE, and PIE compared to individuals of the control group was performed. The statistically significant differences were found only in patients with PIE: 26.92% vs. 83.33% - carriers of the C/ C genotype, 61.54% versus 16.67% - carriers of the C/T genotype and 11.54% versus 0% - carriers of the T/T genotype and 53.85% versus 91.67% - carriers of the G/G genotype, 46 .15% versus 8.33% - carriers of the G/A genotype and 0.0% versus 0.0% - carriers of the A/A genotype, respectively. In addition, in the group of patients with PIE, the distribution of genotype frequencies of the polymorphic variant C3953T of the IL1β gene probably differed from the data of patients with CTE, SVD, and PIE (χ2=28.64; p<0.001), and in the group of patients with CAIE, the distribution of genotype frequencies of the polymorphic variant G308A of the TNFα gene probably differed from the data of patients with SVD and PIE (χ2=24.91; p=0.002). Analyzing the odds ratio and its confidence interval for the genotypes of polymorphic variants C3953T of the IL1β gene and G308A of the TNFα gene in patients with CTE, SVD, CAIE, and PIE, it was established that the presence of the C/T genotype of the IL1β gene increases the risk of encephalopathy in patients with PIE by 8.0 times, and the presence of the G/A genotype of the TNFα gene increases the risk of encephalopathy in patients with PIE by 9.4 times. For the first time in the Ukrainian population, an analysis of the frequency distribution of the genotypes of the polymorphic variant C3953T of the IL1β gene and G308A of the TNFα gene in patients with chronic encephalopathies of various genesis was performed. Statistically, significant differences were found only in patients with PIE compared to healthy individuals. At the same time, the presence of the C/T genotype of the IL1β gene increases the risk of the occurrence and/or progression of PIE by 8.0 times, and the presence of the G/A genotype of the TNFα gene by 9.4 times, which indicates the feasibility of including the corresponding single-nucleotide polymorphisms in the genetic panel of the study patients with PIE.