[THE EXPRESSION OF TLR-4 GENE MONONUCLEAR CELLS PERIPHERAL BLOOO IN PATIENTS BY HIGH RISK OF PURULENT-INFLAMMATORY COMPLICATIONS AFTER SURGERY FOR ACUTE DISEASES OF THE ABDOMINAL ORGANS].

The specified level of gene expression TLR-4 in peripheral blood mononuclear cells in 77 patients operated on acute diseases of the abdominal organs in the 1st and the 4th day after surgery was determined. Established dynamic changes of gene expression TLR-4. Adverse course early postoperative period in patients initially high and medium risk of purulent-septic complications was accompanied by activation of gene expression TLR-4 in peripheral blood mononuclear cells.

[Incidence of odontogenic phlegmon associated with polymorphic variant 896A/G of gene TLR4, but not with 2258G/A of gene TLR2].

The problem actuality is caused by significant enhancement of the incidence rate for inflammatory diseases of the head and neck tissues, first of all of the oral cavity floor abscesses and phlegmons, which causes severe forms of mediastinitis while inadequate treatment. The authors have had established, that Toll-like receptors (TLR) initiate a cascade of anti-inflammatory reactions of the inborn immunity, followed by synthesis of a certain cytokines, and their genetic polymorphism changes the immune reactivity of the organism. Trustworthy correlation of the gene TLR4 (rs4986790) polymorphism 896A/G was proved with high risk of the odontogenic phlegmon of the oral cavity floor occurrence, what would permit to prognosticate the disease course in early terms, to optimize the schemes of its prophylaxis and treatment.

[Polymorphism 896A/G of TLR4 gene rather than 1196C/T and 2258G/A of TLR2 gene determines severe and complicated course of atopic dermatitis in children].

The prevalence of TLR2 gene polymorphisms 2258G/A, 896A/G and 1196C/T of TLR4 gene in children with atopic dermatitis (AD) as compared to the control group has been examined. Results of the distribution analysis of genotypes and alleles of TLR2 and TLR4 genes explicitly show that TLR4 gene mutant allele 896G is detected more frequently in children with AD with increased susceptibility to acute viral respiratory infections (9.3%) as compared to the control group (chi2 = 4.33; p = 0.038). Analysis of association of clinical manifestations of the disease showed a greater frequency of a light flow of blood pressure (p = 0.0001)--the children of AD patients with normal resistance of the organism; a greater frequency of the disease an average severity (p =.0.0033), concomitant allergic rhinitis (AR) and/or bronchial asthma (BA) (p = 0.0355), concomitant AR (p = 0.0673)--in patients with AD with increased susceptibility to acute viral respiratory infections. In AD patients with a mutant allele of the gene TLR4 896G frequently identified: a severe course of disease (p = 0.0485) associated adenoid vegetation in conjunction with AR and/or BA (p = 0.0248), concomitant adenoid vegetation in conjunction with the AR (p = 0.0053) compared with patients with "wild" allele.

[Pharmacogenetic features of the effect of metformin in patients with coronary heart disease in the presence of metabolic syndrome and type 2 diabetes mellitus in terms of PPAR-gamma2 gene polymorphism].

AIM: To define the pharmacogenetic features of the effect of metformin in coronary heart disease (CHD) patients with metabolic syndrome (MS) or type 2 diabetes mellitus (T2DM), by taking into consideration PPAR-gamma2 Pro1 2Ala polymorphism. SUBJECTS AND METHODS: Twenty-four men with CHD and MS and 28 men with CHD and T2DM were examined. The effect of metformin as a short course in combination therapy was evaluated. A population control group consisted of 46 apparently healthy men. The genetic PPRA-gamma2 Pro12Ala polymorphism was studied. A number of indicators (total cholesterol (TC), high-density lipoprotein cholesterol, total lipids, triglycerides, beta-lipoproteins, glycated hemoglobin, C-peptide) and proinflammatory markers, such as interleukin (IL)-1beta, IL-6, IL-8, and tumor necrosis factor-alpha (TNF-alpha) were determined in the blood. RESULTS: Analysis of the frequencies of Pro and Ala alleles indicated a decrease in the latter in CHD patients with T2DM. The CHD and MS patients who carried the Pro allele showed a significant metformin-induced reduction in weight, waist circumference, body mass index, and concentrations of TC, C-peptide, and cytokines, such IL-1beta, IL-6, IL-8, and TNF-alpha. CONCLUSION: Metformin exhibits a high therapeutic efficacy in patients with CHD in the presence of T2DM or MS who have the Pro/Pro genotype, which is of interest in terms of pharmacogenetics and calls for further investigation.

[Quantitative analysis of individual groups of microorganisms, extracted from atherosclerotic lesions in the coronary arteries in patients depending upon ASP299GLY polymorphism of TLR4 gene].

The estimation data of contamination by separate groups of microorganisms and dependence of the microbial content level upon TLR4 gene 896A/G polymorphism in 20 samples of atherosclerotic lesions in coronary arteries has been presented. The presence of TLR4 gene polymorphic allele G in the individual genotype determines the increased contamination of atherosclerotic plaque tissues by the representatives of the following genera: Lactobacillus sp., Enterobacterium sp., Sneathia sp./Leptotrihia sp./Fusobacterium sp., Mobiluncus sp./Corynebacterium sp., Peptostreptococcus sp. The emergence of new correlation pairs with participation of Lachnobacterium sp./Corynebacterium sp. among the carriers of G allele has been revealed via the intragroup correlation analysis. The obtained results confirm the possible involvement of the represented groups of microorganisms in the pathogenesis of atherosclerosis and the role of the TLR4 gene polymorphic variant G in the increased microbial contamination of the coronary arteries tissues.

[Relationship of TLR2 and TLR4 gene polymorphism with a penchant for individual urogenital infections].

We investigated the population prevalence of polymorphisms of Arg753Gln TLR2gene, and Asp299Gly, Thr399Ile TLR4 genes among people living in the Poltava region, as well as data communication polymorphisms with the presence of diseases caused by urogenital infections. The group of population control was a random sample of residents of the Poltava region (n = 299). The group of patients with urogenital diseases included 156 people. Genotyping of these groups TLR2 Arg753Gln polymorphism and the gene TLR4 Asp299Gly, Thr399Ile was performed using PCR and subsequent restriction analysis. Statistically significant association of allele A ofgene TLR2 (p = 0.0018) and allele G of gene TLR4 (p = 0.085) with the presence of urogenital diseases was confirmed.

[Frequency of the Pro 12Ala polymorphism of PPARgamma2 gene in Ukrainian population and its possible role in development of metabolic syndrome].

Frequency of the Pro 12Ala gene polymorphism PPARg2 has been studied in 39 healthy men and 42 men with metabolic syndrome (MS) of the age of 40-65 years in Ukrainian population. The frequencies were 27.9% for 12Ala allele, 32.6% for Pro12Ala, and 4.4% for Ala1Ala that is close to the results of estimation of Czech population. The frequency of 12Ala allele was significantly less--18.4% (p < 0.05) in the persons with MS that corresponds to the pre-established information concerning the patients with diabetes of the 2nd type. A tendency has been detected to the increase of the body mass index in patients with 12Ala allele in the metabolic syndrome group.

[Clinical efficiency of candesartan in patients with renoparenchymal hypertension in dependence on genotype of angeotensin II receptors of I type].

The authors present obtained data on the frequency of genotypes and A and C alleles of polymorphous gene related to Angiotension II first type receptor in patients of Poltava region. These patients were with chronic pyelonephritis and arterial hypertension. Therapeutic efficacy of candesartan treatment of the patients and at the same time their genotypes were considered. Obtained data evidence that AC genotype is more often found among patients with reniparenchymal hypertension, genotype CC is less found among these patients and genotype AA occupies an intermediate place (in 1,7 times less found than among healthy individuals and in 2,2 times more often than among patients with essential hypertension). Candesartan used in monotherapy has a high clinical efficiency in the treatment of patients with AC genotype. Patients with genotype AA and severe course of their disease have to be in a complex treatment or prescribed is applied candesartan in high dosage.

[Polymorphism of the angiotensin II type 1 receptor in patients with essential hypertension in Ukrainian population].

The distribution of polymorphism of the angiotensin II type 1 receptor in Ukrainian population was investigated. Healthy persons had genotypes AA (51%), AC (34%), CC (15%) and alleles A (68%), C (32%). We suppose the prevalence of allele C and genotypes CC in health persons in Ukrainian population. The frequencies of genotypes and alleles in patients with essential hypertension were AA (22,85%), AC (51,9%), CC (25,3%) and A (48,7%), C (51,3%). Thus the development of essential hypertension was associated with the presence of allele C and its homozygote variant. Moreover the severity and complications of hypertension depended on the presence of this allele and genotype. We concluded that Ukrainian population has specific distribution of polymorphism of the angiotensin II type 1 receptor with prevalence of allele C1166 and genotype CC. The presence of these genetic variants is a risk factor for essential hypertension.

[Clinical efficiency of candesatran depends on angiotension II receptor, type 1 gene polymorphism].

Frequency of A and C alleles of the polymorphic gene (A1166C) of first type angiotension II receptor in healthy men of Poltava region was 68% and 32% accordingly, the AA, AC and CC genotypes made up 51%,34% and 15% correspondingly. The patients with essential hypertension had the following figures: 44% and 56%; 23%, 52% and 25% accordingly. The presence of C allele has been established to lead to more severe course and an early development of essential hypertension. Candesatran monoterapy is more effective for treatment patients having C allele.