Increased Frequencies of the ‒174G and ‒572C IL6 Alleles in Populations of Indigenous Peoples of Siberia Compared to Russians.

Abstract-The study of immune response and inflammation gene polymorphisms in a genogeographic context is relevant in the study of human populations. Here, in the indigenous populations of Siberia the frequencies of polymorphic variants ‒174G/C (rs1800795) and ‒572C/G (rs1800796) of the IL6 gene encoding the proinflammatory cytokine IL-6 were determined. For the first time, it was shown that the frequencies of the ‒174G and ‒572C alleles, which determine increased inflammatory response and are also associated with several diseases were statistically significantly higher in ethnic groups of Buryats, Teleuts, Yakuts, Dolgans and Tuvinians than in Russians living in Siberia. These values were in the intermediate position between those in the European and East-Asian groups. We hypothesize an adaptive role of these IL6 genetic variants in human settlement from Africa to the Eurasian continent. However, due to the departure from the traditional way of life and the increasing anthropogenic environmental pollution, the risk of diseases whose pathogenesis is based on inflammation in indigenous Siberian populations is likely increased.

[Increased Frequencies of the -174G and -572C IL6 Alleles in Populations of Indigenous Peoples of Siberia Compared to Russians].

The study of immune response and inflammation gene polymorphisms in a genogeographic context is relevant in the study of human populations. Here, in the indigenous populations of Siberia the frequencies of polymorphic variants -174G/C (rs1800795) and -572C/G (rs1800796) of the IL6 gene encoding the proinflammatory cytokine IL-6 were determined. For the first time, it was shown that the frequencies of the -174G and -572C alleles, which determine increased inflammatory response and are also associated with several diseases were statistically significantly higher in ethnic groups of Buryats, Teleuts, Yakuts, Dolgans and Tuvinians than in Russians living in Siberia. These values were in the intermediate position between those in the European and East-Asian groups. We hypothesize an adaptive role of these IL6 genetic variants in human settlement from Africa to the Eurasian continent. However, due to the departure from the traditional way of life and the increasing anthropogenic environmental pollution, the risk of diseases whose pathogenesis is based on inflammation in indigenous Siberian populations is likely increased.

TCF7L2 gene polymorphism in populations of f ive Siberian ethnic groups.

Investigation of the frequencies of functionally signif icant gene variants in the context of medical biology and gene geography is a relevant issue for studying the genetic structure of human populations. The transition from a traditional to an urbanized lifestyle leads to a higher incidence of civilizational diseases associated with metabolic disorders, including type 2 diabetes mellitus. The goal of the present paper is to analyze the frequencies of functionally signif icant gene alleles in the metabolic prof iles of indigenous Siberian peoples to identify the gene pool resilience, evaluate the susceptibility of various ethnic groups to metabolic disorders under changing environmental conditions, and predict the epidemiological situation that may occur in the near future. The study was performed in the monoethnic samples of eastern and western Buryats, Teleuts, Dolgans, and two territorial groups of Yakuts. A real-time PCR was used to determine the frequencies of single nucleotide polymorphisms (SNPs) G103894T, rs12255372, and C53341T, rs7903146 in the TCF7L2 gene. The results obtained were compared to the frequencies identif ied for Russians from Eastern Siberia and the values available in the literature. The frequencies of the polymorphic variants studied in the samples from the indigenous Siberian peoples place them in between Caucasian and East Asian populations, following the geographic gradient of polymorphism distribution. A signif icantly lower occurrence of type 2 diabetes risk alleles TCF7L2 (103894T) and TCF7L2 (53341T) in the samples of indigenous Siberian peoples compared to Russians was observed, which agrees with their lower susceptibility to metabolic disorders compared to the newcomer Caucasian population. Taking into account urbanization, a reduced growth in type 2 diabetes incidence may be predicted in indigenous Siberian peoples, i. e. Buryats, Yakuts, Dolgans, and Teleuts, compared to the newcomer Caucasian population. A further study of population structure with respect to different metabolic prof ile genes is required to better understand the molecular genetic foundations of the adaptive potential of indigenous Siberian peoples.

[N-aсetyltransferase (NAT2) gene polymorphism and gene network analysis]. / Polimorfizm variantov gena N-atsetiltransferazy 2 (NAT2) i analiz gennoi seti.

To search for new targets of therapy, it is necessary to reconstruct the gene network of the disease, and identify the interaction of genes, proteins, and drug compounds. Using the online bioinformatics tools we have analyzed the current data set related to the metabolism of xenobiotics, mediated by the N-acetyltransferase 2 (NAT2) gene. The study of allelic polymorphism of the NAT2 gene has a prognostic value, allowing to determine the risk of a number of oncological diseases, the degree of increased risk due to smoking and exposure to chemical carcinogens, including drugs. The aim of this study was to determine the frequencies of two important "slow" variants of the NAT2 gene (NAT2*5, rs1801280 and NAT2*7, rs1799931), which significantly affected the rate of xenobiotic acetylation among the indigenous Nenets population of Northern Siberia. The obtained frequencies of polymorphic variants among the Nenets occupy an intermediate value between those for Europeans and Asians, which might indicate specific features of adaptation. We present a model of the distribution of two polymorphic variants of the NAT2 gene involved in the biotransformation of xenobiotics to study the characteristics of their metabolism in the indigenous inhabitants of Yamal.

Role of Nitrogen and Oxygen in Capacitance Formation of Carbon Nanowalls.

Supercapacitors based on carbon nanomaterials are attracting much attention because of their high capacitance enabled by large specific surface area. The introduction of heteroatoms such as N or O enhances the specific capacitance of these materials. However, the mechanisms that lead to the increase in the specific capacitance are not yet well-studied. In this Letter, we demonstrate an effective method for modification of the surface of carbon nanowalls (CNWs) using DC plasma in atmospheres of O2, N2, and their mixture. Processing in the plasma leads to the incorporation of ∼4 atom % nitrogen and ∼10 atom % oxygen atoms. Electrochemical measurements reveal that CNWs functionalized with oxygen groups are characterized by higher capacitance. The specific capacitance for samples with oxygen reaches 8.9 F cm-3 at a scan rate of 20 mV s-1. In contrast, the nitrogen-doped samples demonstrate a specific capacitance of 4.4 F cm-3 at the same scan rate. The mechanism of heteroatom incorporation into the carbon lattice is explained using density functional theory calculations.

Polymorphism of Matrix Metalloproteinases Genes MMP1, MMP2, MMP3, and MMP7 and the Risk of Varicose Veins of Lower Extremities.

We studied the effects of single nucleotide polymorphisms in the promoter regions of matrix metalloproteinase genes rs1799750 (-1607dupG) MMP1, rs243865 (C-1306T) MMP2, rs3025058 (-1171dupA) MMP3, and rs11568818 (A-181G) MMP7 on the risk of varicose vein of the lower extremities in ethnical Russians, residents of the Russian Federation. We genotyped 536 patients with this pathology and 273 healthy participants without history of chronic venous disease. Association was examined using logistic regression analysis. None of the studied polymorphisms showed statistically significant association with the risk of varicose veins of the lower extremities. Our results provide evidence that these polymorphisms are not involved in the pathogenesis of varicose veins and cannot serve as markers of predisposition to this pathology.

[Effect of Bisoprolol on Heart Rate Variability in Patients With Coronary Atherosclerosis: Dependence on Polymorphisms of -1 Adrenergic Receptor Gene].

PURPOSE: To assess effectiveness of a -blocker bisoprolol basing on a study of variability of cardiac rhythm and polymorphism of -1 adrenergic receptor gene (ADRB1). MATERIAL AND METHODS: We examined 99 patients with coronary atherosclerosis either with stable angina without history of vascular events or more than 6 month after myocardial infarction and/or coronary intervention. RESULTS AND CONCLUSION: Patients with coronary atherosclerosis including those after myocardial infarction had signs of autonomic dysfunction regardless of the presence of genetic polymorphism Gly389Arg ADRB1. Sympathetic influences at orthostatic test performed during taking bisoprolol were more pronounced in patients with Gly389Gly ADRB1 genotype than in patients with Gly389Arg ADRB1 genotype. Basing on this observation we conclude that the control by bisoprolol of heart rate regulation in patients with Gly389Gly ADRB1 genotype should be considered inadequate.

Polymorphic Variants rs13155212 (T/C) and rs7704267 (G/C) in the AGGF1 Gene and Risk of Varicose Veins of the Lower Extremities in the Population of Ethnic Russians.

We analyzed associations between single nucleotide polymorphisms (SNP) rs13155212 and rs7704267 in the AGGF1 gene (angiogenic factor with G patch and FHA domains 1) and the risk of risk of varicose veins of the legs in ethnic Russians. Frequencies of alleles, genotypes, and haplotypes were estimated in the sample of patients with this disease (474 patients) and in the control group of participants (478 volunteers) without a history of chronic venous disease. None of the studied polymorphisms was associated with the risk of this pathology. The whole AGGF1 gene sequence lies in a single block of high linkage disequilibrium, and both studied polymorphic variants are representative of all other SNP within this region. From these results, a conclusion was made that AGGF1 gene polymorphism does not affect the risk of varicose veins of the legs in ethnic Russians, or its contribution is low and can be revealed only after analysis of larger cohorts.

CYP1A2 and CYP2D6 Gene Polymorphisms in Schizophrenic Patients with Neuroleptic Drug-Induced Side Effects.

Polymorphic variants of CYP1A2 and CYP2D6 genes of the cytochrome P450 system were studied in patients with schizophrenia with drug-induced motor disorders and hyperprolactinemia against the background of long-term neuroleptic therapy. We revealed an association of polymorphic variant C-163A CYP1A2*1F of CYP1A2 gene with tardive dyskinesia and association of polymorphic variant 1846G>A CY2D6*4 and genotype A/A of CYP2D6 gene (responsible for debrisoquin-4-hydroxylase synthesis) with limbotruncal tardive dyskinesia in patients with schizophrenia receiving neuroleptics for a long time.

[Informativeness of genetic factors for optimization of personalized therapy with clopidogrel].

We studied occurrence of allele variants *1, *2, *3, and *17 of CYP2C19 gene and polymorphic variants of ABCB1 gene in clopidogrel treated patients from West Siberian and Far Eastern regions and determined contribution of these polymorphisms to laboratory efficacy of clopidogrel. In dependence on magnitude of change of platelet aggregation we distinguished groups of patients with different sensitivity to clopidogrel. We found association between polymorphic variant CYP2C19*2 with changes of platelet aggregation after administration of clopidogrel. An additional group of patients with augmented platelet aggregation after administration of clopidogrel was detected. There was no correlation between the latter effect and any of studied polymorphisms.

Magnetofection of human somatic cells with magnetite and cobalt ferrospinel nanoparticles.

Superparamagnetic nanoparticles varying by their chemical composition and synthesis method were used to transfer DNA into somatic cells under the influence of constant magnetic field (method of magnetofection). Magnetite particles obtained by mechanochemical synthesis ensured higher expression of the marker gene GFP (evaluated by fluorescence intensity of the cell lysate) then particles of ferric oxide obtained by chemical co-precipitation and cobalt ferrospinel particles obtained by the mechanochemical method.

Role of polymorphic variants of MTR gene A2756G and SHMT1 gene C1420T in the development of prostatic cancer in residents of the Western Siberian Region of Russia.

Allelic variants of folate cycle enzyme genes can contribute to predisposition to cancer. The impact of polymorphic loci A2756G of MTR gene and of C1420T of SHMT1 gene for the risk of prostatic cancer was studied in residents of West Siberia. The frequency of alleles of these loci in patients (N=371) and controls (N=285) was determined and the data were statistically processed. No statistically significant association with prostatic cancer was detected for any of the studied loci.

[Polymorphic variants of folate metabolizing genes (C677T and A1298C MTHFR, C1420T SHMT1 and G1958A MTHFD) are not associated with the risk of breast cancer in West Siberian Region of Russia].

Breast cancer is the most incident cancer among women. We investigated the role of polymorphisms of folate metabolizing genes MTHFR (C677T and A1298C), SHMT1 (C1420T) and MTHFD (G1258A) in genetic susceptibility to this type of cancer. We determined allele and genotype frequencies in case (850 women with sporadic form of breast cancer) and control (810 women) groups. None of these polymorphisms was significantly associated with breast cancer risk. To increase statistical power of our study, we conducted a meta-analysis which included published genotype data and the results of our work. Meta-analysis also revealed no significant association of studied SNPs with breast cancer.

[Polymorphism of eNOS and iNOS Genes and Chronic Heart Failure in Patients With Ischemic Heart Disease].

UNLABELLED: URGENCY: Despite substantial progress in the treatment of coronary heart disease (CHD) and chronic heart failure (CHF) prognosis in these conditions remains extremely serious. This warrants their timely prevention and early detection. Aim. To study influence of inducible NO synthase (iNOS) (CCTTT)n, Glu298Asp and diallel polymorphism in the fourth intron (4a/4b polymorphism) of endothelial NO synthase gene (eNOS gene) on the state of endothelial function and risk of development of CHF in patients with CHD. MATERIALS AND METHODS: 165 patients with CHD were studied (121 male and 44 female, mean age 56.7 + or - 5.3 years). Vasomotor endothelial function was evaluated using ultrasound method in the reactive hyperemia and trinitroglycerol tests. Genotypes were identified using RFLP analysis of PCR products. Control group consisted of 114 persons (54 male and 60 female, mean age 53.2 + or - 4.9 years). RESULTS: It was determined that the number of repeats of polymorphic locus (CCTTT)n of the iNOS gene and Glu allele of the polymorphic locus Glu298Asp of eNOS gene in the homozygous state were associated with the risk of development of CHD and class of severity of CHF clinical manifestation. In addition Glu allele of the polymorphic locus Glu298Asp of eNOS gene in the homozygous state was associated with the severity and unfavorable development of CHF. The endothelial-dependent dysfunction was more severe in homozygotes of Glu allele of the polymorphic locus Glu298Asp of eNOS gene than in carrier of allele 298Asp. Associations between polymorphic variant of VNTR intron 4 gene eNOS and CHF with the risk of development and endothelial dysfunction were not found. CONCLUSION: An association between polymorphism of iNOS gene (CCTTT)n, eNOS gene (Glu298Asp) with development of CHD and severity of CHF was shown. The polymorphism of eNOS gene (Glu298Asp) was associated with endothelial dysfunction.

[Effect of point substitutions in the MnSOD, GPX1, and GSTP1 genes on the risk of familial and sporadic breast cancers in residents of the Altai region of the Russian Federation].

The frequencies of the polymorphic gene variants MnSOD Ala9Val, GPX1 Pro198Leu, and GSTP1 Ile105 Val were estimated in female residents of Altai krai with breast cancer. The frequency distributions of the genotypes for all genes studied in both patients and control subjects fit the Hardy-Weinberg equilibrium. The estimated frequencies of the genotypes for the studied genes in the control group did not differ from those earlier reported for Caucasoid women living in Europe. The T(rs1050450) allele of the GPX1 gene was demonstrated to protect against sporadic breast cancer (OR = 0.74 (95% CI = 0.58-0.94), p = 0.012). Carriers of the genotype combination MnSOD CC + GPX1 CC were found to have a 1.6 times higher risk of sporadic breast cancer compared to the control group (OR = 1.59 (1.05-2.41), p = 0.0258). The polymorphic loci GSTP1 (rs1695) and MnSOD (rs4880) were not found to be significantly associated with the risk of familial or sporadic breast cancer.

[Impact of Gly389Arg beta1-adrenoceptor polymorphism on the risk of chronic heart failure, the nature of its course, and on the efficiency of its treatment with carvedilol].

AIM: To study beta1-adrenoceptor gene (ADRB1) polymorphism on the development and course of chronic heart failure (CHF) and on the efficiency of its treatment with the beta-adrenoblocker carvedilol in patients with coronary heart failure. SUBJECTS AND METHODS: Two hundred and twenty-six patients (149 males and 77 females; mean age 55.9 +/- 5.8 years) with CHF, who received continuous basic therapy: angiotensin-converting enzyme inhibitors, a diuretic, an aldosterone antagonist, digoxin, and a beta-adrenoblocker, were examined; 68 patients were given for 24 weeks carvedilol (its starting dose was 3.125 mg twice daily with its further adjustment until an individually tolerable dose was achieved). Genotypes were identified by the restriction fragment length polymorphism analysis of polymerase chain reaction products. A control group comprised 136 subjects (63 males and 73 females; mean age 55.9 +/- 5.8 years) without signs of cardiovascular disorders, as evidenced by the examination. RESULTS: In patients with CHF, the Gly allele of the Gly389Arg polymorphic locus of the ADRB1 gene in homozygous state was associated with the high individual risk for CHF, the severity of its clinical manifestations and the nature of its course while carriage of the Arg allele of the Gly39Arg polymorphic locus manifested itself as a protective factor. During long-term carvedilol therapy, CHF patients with the Arg/Arg genotype of the ADRB1 gene were observed to have a more pronounced decrease in the functional class of heart failure, a significant increase in left ventricular ejection, and a decrease in left ventricular end-systolic and end-diastolic sizes as compared with patients with the Gly/Arg genotype. CONCLUSION: There were associations of the polymorphism of ADRB1 gene (the Gly39Arg polymorphic locus) with the development and severity of CHF and with the efficacy of therapy with beta-adrenoblocker carvedilol.

Associations of polymorphic variant of MnSOD gene with breast cancer in residents of the Altai Region.

he incidence of MnSOD genotypes in residents of the Altai Region suffering from breast cancer and individuals without a history of cancer corresponded to the Hardy-Weinberg equilibrium. No association of MnSOD with the incidence of sporadic breast cancer was detected. No association of MnSOD, tobacco smoking, or menopausal status, on the one hand, and breast cancer development, on the other, was detected.

[The features of myocardial infarction clinical course at gene of endothelial NO-synthase polymorphisms].

81 patients were included in the research into study of acute myocardial infarction (AMI) clinical course features in patients with various polymorphism of gene. These patients besides traditional examination, received genetic examination for determination of of NO-synthase gene in intron 4 (eNOS 4a/4b polymorphism) and mutation in position 298 of protein sequence leading to replacement of rest of glutamine acid by asparaginic acid (Glu298Asp). Patients with allele 4a polymorphism of endothelial NO-synthase gene in intron 4 (genotypes 4a/4a and 4a/4b) had low level of high-density lipoprotein cholesterol (HDLC) in comparison with 4b homozygote patients. Inverse association of 4a allele with HDLC did not depend on the AMI therapy character. Besides, it was detected that AMI patients with 4a/4a polymorphism had bronchial asthma and chronic hepatitis more frequently than patients with 4b/4b genotype. AMI patients with 4a allele had early postinfarction angina and gastroesophagoreflux disease. The relation of allele 4a carriage with development of early postinfarction angina depended on presence of bronchial asthma in AMI patients. AMI patients with Glu298Asp polymorphism Asp/Asp genotype did not have significant differences in AMI and concomitant pathology course in comparison with Glu/Glu genotype patients.

[Transcription factor YY1 participates in activation transcription of the human ribosomal protein L11 gene].

Ribosomal protein L11 plays important role in ribosome, being involved in several steps in protein synthesis and also activates p53-dependent cell cycle arrest. Changes in the rpL11 levels might be implicated in cell cycle control and carcinogenesis. Therefore, the mechanism of regulation of rpL11 expression has increasing importance. Article presents research results of interaction of promotor elements of gene HRPL11 with proteins of nuclear extracts of cells of a various cell origin. Use oligonucleotide competitors containing known transcription factor-binding sites, and also polyclonal antibodies has shown, that transcription factor YY1 participates in regulation of a transcription of gene HRPL11 in all investigated cellular lines. Our data obtained from comparison of protein binding profiles using nuclear extracts from rapidly growth cells, normal cell lines and serum deprivation repressed cell allows us to consider of transcription factor YY1 as activator of HRPL11 gene transcription.

[Association of methylenetetrahydrofolate reductase gene polymorphism with the development of myocardial infarction in patients with type 2 diabetes].

A hundred and eighteen patients aged 45-60 years who had type 2 diabetes (T2D) with and without coronary heart disease (CHD) were examined to study the frequency of the methylenetetrahydrofolate reductase (MTFR) C677T gene polymorphism in T2D and its association with the level of homocysteine (HC) and the development of myocardial infarction (MI). A control group included 89 blood donors. Statistically significant differences were found in the frequency of alleles T677 and C677, genotype C677C between the groups of patients with T2D, CHD, and prior MI and the control group. Allele T677 of the MTFR gene was associated with a higher risk of MI in patients with T2D (OR = 1.879; p = 0.029). A combination of genotype T677T of the MTFRgene with hyper-homocysteinemia in patients with T2D is closely related to other risk factors of cardiovascular diseases and may have a significant impact on the course of CHD.