Analysis of the Association of TNF -238G>A Gene Polymorphism with the Risk of Rheumatoid Arthritis Development in Russian Population in the Republic of Karelia.

We studied association of the TNF gene -238G>A polymorphism (rs361525) with the risk of rheumatoid arthritis development in the Russian population living in the Republic of Karelia. The influence of rs361525 on the development of rheumatoid arthritis was revealed: genetic predisposition to this disease is associated with the presence of GG genotype. The effect of the genotype on the polymorphic locus of -238G>A on TNF mRNA content was revealed. Increased content of transcripts of this gene is associated with the presence of A allele.

[Analysis of an association of TNF -308G>A polymorphism with a risk for pulmonary sarcoidosis in the Russian population of the Republic of Karelia]. / Analiz assotsiatsii polimorfizma -308G>A gena TNF s riskom razvitiya sarkoidoza legkikh u russkogo naseleniya Respubliki Kareliya.

AIM: To analyze an association of TNF -308G>A polymorphism with a risk for pulmonary sarcoidosis (PS) in the Russian population of the Republic of Kareli. SUBJECTS AND METHODS: 84 patients with persistent PS and 96 donors without clinical manifestations of this disease (a control group) were examined. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis was used to identify alleles and genotypes by the marker of TNF -308G>A polymorphism. The level of transcripts of the above gene in the peripheral blood leukocytes of healthy and sick people was determined by real-time PCR. RESULTS: There were no significant differences in the distribution of allelic and genotypic frequencies by the marker of TNF -308G>A polymorphism between the control and PS patient groups. There was a significant increase in the number of TNF gene transcripts in the peripheral blood leukocytes of patients with PS compared to the controls. At the same time, there were no marked differences in mRNA expression levels in the above gene in the carriers of different genotypes by the marker of TNF -308G>A polymorphism in all the examined groups. CONCLUSION: The marker of TNF -308G>A polymorphism is unassociated with the risk of PS in the Russian population of the Republic of Karelia. No differences in TNF mRNA levels in the carriers of different genotypes by the above marker may suggest that the found elevated level of transcripts in the above gene in patients with diagnosed with PS is due to the development of the body's inflammatory responses in this disease.

[Subpopulations of Regulatory T-lymphocytes in the Peripheral Blood of Patients with Rheumatoid Arthritis].

BACKGROUND: Rheumatoid arthritis (RA) is an inflammatory rheumatic disease associated with a dysfunction of the T cell-mediated tolerance and leading to the disability of working population. The regulatory CD4' T cells play an important role in the regulation of autoimmunity and can suppress immune responses. With that, there is no consensus on the content of these lymphocytes and their role in the pathogenesis of RA. Objective: The aim of the study was to assess the content ofperipheral blood regulatory Tcells (Treg) according to the expression of membrane markers CD4, CD25, CD127 and intracellular FOXP3 marker, as well as the expression of two functional molecules (CTLA-4 and CCR4) in Treg cells of patients with RA. METHODS: Peripheral blood samples of RA patients (median age 65,5 years [54;68,3) and healthy controls (median age 58 years [44; 66]) were analyzed. Cell count and the expression level of molecules were assessed by flow cytometry. RESULTS: Peripheral blood samples of 36 RA patients and 20 healthy donors were analyzed. The number of the cells with Treg-associated phenotypes CD4⁺CD25hi and CD4⁺CD25hiCD127low/⁻ was higher in RA patients in comparison with healthy donors. Increased levels of RA CD4⁺ T cells expressing FOXP3 were also observed. This may be due to increasing in the number of CD4⁺FOXP3⁺CD25⁻ lymphocytes, whereas the content of RA CD4⁺FOXP3⁺CD25⁺ Treg cells was at the level of the control. The expression of the functional molecule CTLA-4 in Treg cells of patients with RA was not different from the control, while the expression level of the chemokine receptor CCR4 which provides migration of lymphocytes at sites of inflammation and barrier tissues was significantly increased in RA patients. CONCLUSION: Increase in the levels of certain Treg-associated lymphocyte populations were detected in peripheral blood of RA patients. During the natural course of RA, alterations in the level of the chemokine receptor CCR4 might indicate the enhanced lymphocyte migration.

[A CASE OF SEVERE AMLODIPINE POISONING].

The article is devoted to the actual problem--poisoning by calcium channel blockers. The case of the departure of the patient amlodipine, clinical picture, treatment and its effectiveness. In the discussion described pharmacological characteristics of the group of calcium channel blockers, mechanisms of development syndromes developing in this type of shipment and pathogenetic approach to therapy.