The CXCR2 Gene Polymorphism Is Associated with Stroke in Patients with Essential Hypertension

Hypertension is the major risk factor for stroke, and genetic factors contribute to its development. Inflammation has been hypothesized to be the key link between blood pressure elevation and stroke. We performed an analysis of the association between inflammatory mediator gene polymorphisms and the incidence of stroke in patients with essential hypertension (EH). The study group consisted of 625 individuals (296 patients with noncomplicated EH, 71 hypertensive patients with ischemic stroke, and 258 control subjects). Both patients and controls were ethnic Tatars originating from the Republic of Bashkortostan (Russian Federation). The analysis has shown that the risk of ischemic stroke was associated with the CXCR2 rs1126579 polymorphism. Our results indicate that among patients with EH, the heterozygous genotype carriers had a higher risk of stroke (OR = 1.72, 95% CI 1.01-2.92), whereas the CXCR2*C/C genotype was protective against stroke (OR = 0.32, 95% CI 0.12-0.83). As shown by the gene-gene interaction analysis, the CXCR2 rs1126579 polymorphism was also present in all genotype/allele combinations associated with the risk of stroke. Genetic patterns associated with stroke also included polymorphisms in the CCL2, CCL18, CX3CR1, CCR5, and CXCL8(IL8) genes, although no association between these loci and stroke was detected by individual analysis

Association of obesity susceptibility gene variants with metabolic syndrome in women

Aim. The aim of the study was a replicative analysis of the association of polymorphic variants of genes associated with obesity revealed by results of wide-genomic studies (GWAS) with the development of a cluster of metabolic syndrome risk parameters in women of Bashkir and Tatar ethnicity. The polymorphic markers of the following genes were analyzed: SEC16B, FADS1, KCTD15, MAF, MAP2K5, NEGR1, BDNF, TMEM18. Materials and methods. The study involved 243 women with metabolic syndrome and 298 women without the metabolic syndrome. Amplification of DNA fragments was performed using real-time PCR and TaqMan technique. Results. We found the association the metabolic syndrome with genetic markers of genes MAF and TMEM18 from Tatar. Protective informative marker of the metabolic syndrome among Tatar and Bashkir was the TT haplotype TMEM18 gene (rs2860323 and rs6548238) (р=0.005 and р=0.001, respectively). We identified the association marker rs2241423 MAP2K5 gene with the level of waist circumference (p=0.003) and with the level of cholesterol (p=0.014), the marker rs11084753 KCTD15 gene with glucose levels after exercise (p=0.002), the level of triglycerides (p=0.003) and HDL (p=0.0008) among Tatar women. We identified the association rs2241423 MAP2K5 gene marker to glycated hemoglobin level (p=0.002) and a marker gene rs174550 FADS1 with triglyceride levels (p=0.02) among Bashkir women. Conclusion. It can be assumed that the polymorphic variants FADS1, KCTD15, MAF, MAP2K5, TMEM18 genes are an important part of the genetic structure of predisposition to metabolic syndrome and/or to a cluster of clinical and biochemical indicators of the risk of metabolic syndrome

The association of TCF7L2 rs7903146 polymorphism with type 2 diabetes mellitus among Tatars of Bashkortostan

Aim. To perform the analysis of the association of transcription factor 7-like 2 (TCF7L2) gene rs7903146 polymorphism with type 2 diabetes mellitus (T2DM) among Tatars of Bashkortostan. Materials and methods. In this study, 169 patients with T2DM and 286 controls without clinical symptoms and laboratory signs of diabetes and without diabetes relatives were examined. Amplification of the DNA fragments was performed using real-time polymerase chain reaction (PCR) and TaqMan technique. Results. Genotype CT and allele T ratios were higher in the T2DM group than in controls (46. 7% vs. 36. 4%, p = 0. 030; 41. 7% vs. 30. 8%, p = 0. 001 respectively). There was a positive association between allele T and T2DM (OR = 1. 61), and allele C had a protective effect (OR = 0. 62, p = 0,001). Carriers of the ТТ genotype had later onset of T2DM (mean = 59. 5 years old) compared with carriers of the CT and CC genotypes (56. 1 years old, p = 0. 044). Basal C-peptide concentration, lipid levels and body mass index were not associated with TCF7L2 rs7903146 polymorphism. Conclusion. TCF7L2 rs7903146 polymorphism is associated with T2DM among Tatars of Bashkortostan

Polimorfizm gena glavnogo kompleksa gistosovmestimosti klassa II DRB1 i risk razvitiya sakharnogo diabeta tipa 1 v etnicheskikh gruppakh Bashkortostana

Цель: исследования состояла в изучении роли по? лиморфизма гена HLA класса II DRB1 в формировании наследственной предрасположенности к СД ти? па 1. Объем и методы: Обследовано 186 больных СД типа 1. Контрольная группа была сформирована из 71 мужчины и 100 женщин без клинических признаков диабета. Образцы ДНК были получены из венозной крови методом фенольно-хлороформной экстракции. Результаты: при сравнении полученных нами результатов с данными других авторов обращает на себя внимание тот факт, что в популяциях башкир, русских и татар Башкортостана выявлены те же самые специфичности риска (DRB1*04 и DRB1*17) и антириска (DRB1*15), что и в других популяциях eвропеоидов и монголоидов

Multilocus associations of inflammatory genes with the risk of type 1 diabetes

BackgroundGenome-wide association studies have captured a large proportion of genetic variation related to type 1 diabetes mellitus (T1D). However, most of these studies are performed in populations of European ancestry and therefore the disease risk estimations can be inaccurate when extrapolated to other world populations.MethodsWe conducted a case-control study in 1866 individuals from the three major populations of the Republic of Bashkortostan (Russians, Tatars, and Bashkirs) in Russian Federation, using single-locus and multilocus approach to identify genetic predictors of T1D.ResultsWe found that LTA rs909253 and TNF rs1800629 polymorphisms were associated with T1D in the group of Tatars. Meta-analysis of the association study results in the three ethnic groups has confirmed the association between the T1D risk and LTA rs909253 genetic variant. LTA rs909253 and TNF rs1800629 loci were also featured in combinations most significantly associated with T1D.ConclusionOur findings suggest that LTA rs909253 and TNF rs1800629 polymorphisms are associated with the risk of T1D both independently and in combination with polymorphic markers in other inflammatory genes, and the analysis of multi-allelic combinations provides valuable insight in the study of polygenic traits

Vaccine-associated paralytic poliomyelitis in a child: fast transformation from Sabin-like virus to vaccine-derived poliovirus triggered an epidemiological response in two countries of the European region

Objectives: The detection of a vaccine-derived poliovirus (VDPV) requires an epidemiological assessment and response. Using repeated stool sampling from a child who is immunocompetent and was vaccinated against poliomyelitis with acute flaccid paralysis, a case of an extremely rapid evolution of Sabin-like poliovirus (PV) type 3 was traced in the child's body. Methods: The case was independently identified in two countries—Tajikistan and Russia. Stool samples for the study were also independently collected in two countries on different days from the onset of paralysis. Virological, serological, and molecular methods; full genome Sanger; and high-throughput sequencing were performed to characterize isolates. Results: PV isolates from samples collected on days 2, 3, and 14 contained eight, seven, and seven mutations in the VP1-coding region, respectively, and were classified as Sabin-like PV type 3. The isolates from samples collected on days 15 and 18 had 11 mutations and were classified as vaccine-derived PVs, which required an epidemiological response in the two countries. Conclusion: The results indicate the need to continue acute flaccid paralysis surveillance, maintain high vaccination coverage, and develop and introduce new effective, genetically stable PV vaccines

Variants of the Coagulation and Inflammation Genes Are Replicably Associated with Myocardial Infarction and Epistatically Interact in Russians.

In spite of progress in cardiovascular genetics, data on genetic background of myocardial infarction are still limited and contradictory. This applies as well to the genes involved in inflammation and coagulation processes, which play a crucial role in the disease etiopathogenesis.In this study we found genetic variants of TGFB1, FGB and CRP genes associated with myocardial infarction in discovery and replication groups of Russian descent from the Moscow region and the Republic of Bashkortostan (325/185 and 220/197 samples, correspondingly). We also found and replicated biallelic combinations of TGFB1 with FGB, TGFB1 with CRP and IFNG with PTGS1 genetic variants associated with myocardial infarction providing a detectable cumulative effect. We proposed an original two-component procedure for the analysis of nonlinear (epistatic) interactions between the genes in biallelic combinations and confirmed the epistasis hypothesis for the set of alleles of IFNG with PTGS. The procedure is applicable to any pair of logical variables, e.g. carriage of two sets of alleles. The composite model that included three single gene variants and the epistatic pair has AUC of 0.66 both in discovery and replication groups.The genetic impact of TGFB1, FGB, CRP, IFNG, and PTGS and/or their biallelic combinations on myocardial infarction was found and replicated in Russians. Evidence of epistatic interactions between IFNG with PTGS genes was obtained both in discovery and replication groups

The map of possible interactions between components of MI-associated biallelic combination <i>IFNG</i> and <i>PTGS1</i> (black circles) and ten relative partners (gray circles) generated by GeneMania online software [45].

<p>Possible physical interactions (pink), co-expression (violet), pathway (blue), genetic interactions (green), and shared protein domains (yellow) are shown. IDO1 –indoleamine 2,3–dioxygenase 1; IFNG–interferon gamma; IFNGR1 –interferon gamma receptor 1; IFNGR2 –interferon gamma receptor 2; IRF1 –interferon regulatory factor 1; MPO–myeloperoxidase; PTGIS–prostaglandin I2 (prostacyclin) synthase; PRKCD–protein kinase C delta; PTGS1 –prostaglandin–endoperoxide synthase 1; PTGS2 –prostaglandin–endoperoxide synthase 2; PTPN2 –protein tyrosine phosphatase, non–receptor type 2; PTPN6 –protein tyrosine phosphatase, non–receptor type 6.</p

Predictors of Progression and Mortality in Patients with Chronic Hypersensitivity Pneumonitis: Retrospective Analysis of Registry of Fibrosing Interstitial Lung Diseases

Hypersensitivity pneumonitis (HP) is an interstitial lung disease (ILD) resulting from an immune-mediated response in susceptible and sensitized individuals to a large variety of inhaled antigens. Chronic HP with a fibrotic phenotype is characterized by disease progression and a dismal prognosis. The aim of this study was to identify predictors of progression and mortality in patients with chronic HP in real clinical practice. Materials and methods: This retrospective, multicenter, observational study used data from a registry of 1355 patients with fibrosing ILDs. The study included 292 patients diagnosed with chronic HP based on the conclusion of a multidisciplinary discussion (MDD). Results: The patients were divided into groups with progressive (92 (30.3%) patients) and nonprogressive pulmonary fibrosis (200 (69.7%) patients). The most significant predictors of adverse outcomes were a DLco < 50% predicted, an SpO2 at the end of a six-minute walk test (6-MWT) < 85%, and a GAP score ≥ 4 points. Conclusion: Pulmonary fibrosis and a progressive fibrotic phenotype are common in patients with chronic HP. Early detection of the predictors of an adverse prognosis of chronic HP is necessary for the timely initiation of antifibrotic therapy

ROC curves demonstrate usefulness of the additive composite model built from all identified genetic markers.

<p><b>A</b>. Comparing performance of the composite model to the performance of each single marker in the Moscow discovery sample. Combining the high specificity of <i>CRP</i> and <i>IFNG</i>+<i>PTGS</i> predictors (the left hump) with relatively high sensitivity of <i>TGFB1</i> and <i>FGB</i> (the right hump) yields a much better classifier. <b>B</b>. Performance of the model stays the same when tested on the independent replication sample (Bashkortostan).</p