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Khodyrev D.S.,Federal Research Clinical Center for Specialized Types of Health Care and Medical Technologies | Nikitin A.G.,Federal Research Clinical Center for Specialized Types of Health Care and Medical Technologies | Brovkin A.N.,Federal Research Clinical Center for Specialized Types of Health Care and Medical Technologies | Lavrikova E.Y.,Federal Research Clinical Center for Specialized Types of Health Care and Medical Technologies | And 6 more authors.
Diabetes Mellitus | Year: 2015

The study of hereditary predisposition to multifactorial diseases is essential for diagnosis and selection of the optimal treatment. The study of polymorphisms of candidate genes whose products are involved in the pathogenesis of multifactorial diseases is of great clinical importance. Aim. The aim of this study was to investigate the association of rs2241766 and rs1501299 polymorphisms in the ADIPOQ gene, rs2275737 and rs2275738 polymorphisms in the ADIPOR1 gene and rs11061971 and rs16928751 polymorphisms in the ADIPOR2 gene with the development of type 2 diabetes mellitus (T2DM) in the Russian population. Materials and methods. The study included a group of 500 patients with T2DM diagnosed based on standard diagnostic criteria (T2DM+). The control group (T2DM-) was a random sample of 500 patients with no evidence of the disease and was matched to the T2DM+ group for gender, age and body mass index. The determination of alleles and genotypes was performed using real-time polymerase chain reaction with TaqMan probes. The χ2 test and contingency tables were used to compare the distribution of allele and genotype frequencies. A p-value of <0.05 was considered to be statistically significant. Results. Comparative analysis of the distribution of alleles and genotypes indicated an association between T2DM and the disease gene polymorphic marker rs11061971 ADIPOR2 (p = 0.004 for the distribution of alleles, p = 0.011 for the distribution of genotypes). The presence of allele A and genotype AA decreased the risk of development of T2DM (OR = 0.76 and 0.75, respectively), whereas the T allele carriers and TT genotype were associated with an increased risk of developing T2DM (OR = 1.31 and 1.63, respectively). There was no statistically significant association between T2DM and polymorphic markers of ADIPOQ or ADIPOR1 genes. Conclusions. Based on this data, polymorphism of the ADIPOR2 gene in the Russian population is associated with the development of T2DM, but there is no association between T2DM and polymorphism of the ADIPOQ or ADIPOR1 genes.


Lebedeva N.O.,Moscow State University | Vikulova O.K.,Moscow State University | Nikitin A.G.,Federal Research Clinical Center for specialized types of health care and medical technologies | Shamkhalova M.S.,Endocrinology Research Center | And 2 more authors.
Diabetes Mellitus | Year: 2016

Aim. To investigate the association of variation in lipid-lowering response and endothelial function (EF) parameters after atorvastatin therapy in patients with type 2 diabetes mellitus (T2DM) with genetic markers of atherosclerosis. Methods. We included 97 patients with T2DM who were prescribed atorvastatin. Fasting lipid profiles and EF parameters were assessed before and after 12 months of statin therapy. For EF evaluation, we performed pulse-wave analysis during reactive hyperaemia. The genotypes for polymorphic markers were identified by real-time polymerase chain reaction with TaqMan probes. The statistical analysis included Wilcoxon, Mann-Whitney and Kruskal-Wallis tests. P-values < 0.05 were considered statistically significant. Results. With statin therapy, PPARG2Pro/Pro patients had significantly lower TC and LDL-C levels than PPARG2 Pro/Ala and PPARG2 Ala/Ala patients (TC: 20.74% vs. 4.6% and 5.61%; p = 0.04 and LDL-C: 26.00% vs. 6.11% and 7.32%; p = 0.029). Patients with APOEE4/E4 had significantly lower TC and TG levels than other APOE patients (TC: -46.25% for E4/ E4 vs. +33.33% for E4/E2, +5.73% for E3/E2, +11.80% for E3/E4, -10.92% for E3/E3, p = 0,01; TG: -56.52% for E4/ E4 vs. +24.43% for E4/E2, +19.63% for E3/E2, +8.05% for E3/E4, -20.00% for E3/E3, p = 0.04). The patients with GG for TNFα G(238)A and GA for TNFα G(308)A had significantly greater amplitude of post-occlusive wave increase (Apw) than patients with GA for TNFα G(238)A and GG for TNF G(308)A (+8.16 % vs. -0.93%, E = 0,04; +44% vs. -4.4%, p = 0.004, respectively). Conclusion. PPARG2Pro12Ala and APOEE E2/E3/E4 polymorphism contributed to the between-patient variability in the response to statin therapy in patients with T2DM. Significant associations of the TNFα gene polymorphism with EF in patients with T2DM suggest an important role of inflammation in the pathogenesis of MVD. © Russian Association of Endocrinologists, 2016.


Ardashev A.V.,Institute of Postgraduate Education of Federal Biomedical Agency | Mazurov M.E.,Moscow State University | Zhelyakov E.G.,Institute of Postgraduate Education of Federal Biomedical Agency | Kalyuzhniy I.M.,Moscow State University | And 2 more authors.
Kardiologiya | Year: 2015

Aim: To compare the theoretical possibility of permanent atrial fibrillation (AF) elimination (on the model of the 6-wave re-entry) result of ablative formatting and subsequent electrical cardioversion and to compare the obtained data with the results of electrophysiological studies, ablation and clinical follow up of patients with permanent AF. Material and methods. Clinicall phase. Study was conducted on consecutive 20 pts (6 women, 51.4 ± 13.6 years of age) with permanent AF who underwent index ablation which consisted of antral isolation of PVs, mitral isthmus and roof ablation, and posterior wall of left atrium substrate modification. We evaluated AF CL into the coronary sinus during procedure. Mathematical phase. As the first step numeric reconstruction of the autowave process in excitable tissues of the LA and the simulation of 6-wave re-entry AF was performed using Fitzhugh-Nagumo equation. A special scanning method was used for calculating characteristics of autowave processes in a 2D mathematical model of the LA. Then ablation formatting which corresponding all ablation lines was performed. Modeling of cardioversion applied for 6- And 4-wave re-entry. Results. Clinical phase. Organization of AF CL (from 112 ±24 to 204±35 ms) was verified in 16 of 20 pts after ablation. SR was effectively restored after external cardioversion in the end of procedure in all pts. Mathematical phase. Ablation formatting (corresponding to linear ablation) may transform 6-wave reentry to 4 wave re-entry. Following simulation of cardioversion may effectively terminate 4-wave AF, whereas did not terminate 6-wave reentry AF. Conclusion. Ablative formatting performed on the mathematical model of permanent AF leads to the transformation of the 6-wave re-entry in 4-wave. Subsequent mathematical modeling of electrical cardioversion terminates 4-wave re-entry with impossibility of it renewal. Clinical results are consistent with ablation formatting data obtained by means of 6-waves re-entry simulation in 2D mathematical modeling of the LA.


Volchkova E.A.,Moscow Medical Academy | Nikitin A.G.,Federal Research Clinical Center for Specialized Types of Health Care and Medical Technologies | Zotova I.V.,Moscow Medical Academy | Zateyshchikova A.A.,Clinical Hospital No51 | And 4 more authors.
Kardiologiya | Year: 2015

It can be suggested that development of atrial fibrillation (AF) in patients with chronic obstructive pulmonary disease (COPD) is directly related to the system of inflammation. Genetic polymorphism of factors of this system can be one of components of mechanism of AF in COPD. Aim: To elucidate polymorphic markers of genes of factors of the system of inflammation associated with AF in patients with COPD. Material and methods. We examined 208 patients with COPD (52 with and 156 without AF). Examination included spirometry, echocardiography, and study of frequencies of polymorphic markers G(-238)A, G(-308)A of tumor necrosis factor (TNF) gene, C(-819)T of interleukin (IL) 10 gene, G(-174)C of IL-6 gene, rs2228145(A/C) of IL-6R gene, and rs2069762(A/C) of IL-2 gene. Results. Factors associated with AF were left atrial volume (odds ratio [ORJ 1.021, 95% confidence interval [CI] 1.004-1.043, p=0,027), right atrial volume (OR 1.02, 95% CI 1.001-1.040, p=0.021), and carriage of C allele of polymorphic marker G(-174)C of IL-6 gene (OR 6.02, 95% CI 1.87-19.38, p=0.003). Conclusion. C allele of polymorphic marker G(-174)C of IL-6 gene can be considered to be independently associated with development of AF in patients with COPD.

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