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Objective. To assess the association of single nucleotide polymorphisms of genes potentially involved in the comorbidity of bronchial asthma (BA) and essential hypertension (HTN) in patients with different time onset of the diseases.Design and methods. Genotyping of 92 SNPs was performed using MALDI-TOF mass spectrometry in patients with BA and HTN (n = 97) and healthy individuals (n = 153). The group of patients with comorbid pathology was divided into two subgroups depending on the time of onset of symptoms of BA relative to HTN, and the prevalence of all studied SNPs was compared in each subgroup relative to the control.Results. The variant rs11590807 regulating expression for UTP25, TRAF3IP3, C1orf74, HSD11B1-AS 1, IRF6 genes in the heart, blood vessels, and lung is associated with BA and HTN, regardless of the time onset of each of these diseases. Associations of other variants are specific with respect for each subgroup of comorbid diseases. The rs1010461 variant, which regulates the expression of RNASE4 and ANG genes, is linked with HTN as the first phenotype of the comorbidity. The rs769214, rs11032700, rs11032699, rs484214, and rs480575 variants, which regulate the expression of CAT gene, are associated with BA as the first phenotype of disease comorbidity.Conclusions. We found specific associations of the studied polymorphic variants in the development of comorbid phenotypes of BA and HTN, which differ in the time of manifestation of each of the diseases relative to each other.

Hypertension, coronary heart disease, myocardial infarction, obesity, and type 2 diabetes mellitus are common comorbidities in patients with bronchial asthma. The causes for developing these diseases are multifactorial and involve inherited genetic factors. However, little is known about the genes contributing to the development of comorbidities in bronchial asthma and cardiovascular disease continuum.Objective. To examine the associations of genetic polymorphic variants potentially involved in the development of bronchial asthma comorbid with hypertension, coronary heart disease, type 2 diabetes mellitus, and obesity.Material and Methods. Genotyping of 92 single nucleotide polymorphisms (SNPs) was performed using MALDI-TOF mass spectrometry in patients with bronchial asthma associated with cardiovascular/metabolic disorders (n = 162) compared with a control group of apparently healthy individuals (n = 153).Results. The development of bronchial asthma phenotypes comorbid with cardiovascular/metabolic disorders was associated with the particular genetic variants affecting the expression of genes including CAT, TLR4, ELF5, ABTB2, UTP25, TRAF3IP3, NFKB1, LOC105377347, C1orf74, IRF6, and others in the target organs of study disease profile. Only one SNP (rs11590807), which is regulatory for the UTP25, IRF6, TRAF3IP3, and RP1-28O10.1 genes, was associated with all studied comorbid phenotypes of bronchial asthma and diseases of cardiovascular continuum.Conclusion. The obtained results demonstrated that the identified SNPs affecting the expression of many genes may serve as potential biological markers of complex causal relationships between bronchial asthma and cardiometabolic disorders.

The activating research interest in the problem of tuberculosis development is due to the increase in cases of drug resistance, coinfection with HIV and hepatitis, and the lack of an effective vaccine. However, the pathogenesis of tuberculosis remains insufficiently studied at present. A significant role is assigned to hereditary factors, as the majority of those infected with Mycobacterium tuberculosis remain resistant to tuberculosis, and only in 5—15% of cases does infection lead to the development of the disease. Despite a long history of research of genetic factors of susceptibility to tuberculosis infection — from the search for monogenic forms of immune dysfunction, associations of individual tuberculosis susceptibility genes, to the analysis of genome-wide associative studies and the assessment of the characteristics of the transcriptional profiles of patients, — the problem of obtaining clinically significant results for the identification and monitoring of risk groups remains particularly acute. The search of differentially expressed genes in groups with different status of the disease (non-infected, latent tuberculosis infection, presymptomatic state, active tuberculosis, recovery from tuberculosis, non-tuberculosis infection) led to identification of a large number of data which is not overlapped in different compared groups, different ethnic groups, in the studies of the whole blood and cellular models. Merging this wealth of data followed by its reanalysis helps to verify and update results. However, there still is a large number of questions concerning our understanding of the functioning of the human organism under the influence of M. tuberculosis. In recent years, new approaches have been used to develop test systems for the diagnosis of various forms of the disease. The review considers up to date results of expression studies of susceptibility to tuberculosis, namely, objects and approaches of research changing over time, forms of the host response to the mycobacteria infection studied, the influence of different factors on the results.

The simultaneous development of several diseases (comorbidity, syntropy) in particular patients is a common phenomenon in modern clinical practice. However, the results of recent epidemiological studies have pointed to the new phenomenon of inverse comorbidity (or dystropy)—that means that some diseases can occur together in one person more rarely than in other people according to frequencies of these disorders in the population as a whole. Such dystropic (inversely comorbid) diseases are Huntington’s disease and oncological ones. In this paper, we perform a review of existing information supporting the hypothesis of the oncoprotection in carriers of HTT mutation, also including features of interactions of genes and proteins in such processes as autophagy and apoptosis.

Specificity of the structure of gene pools of different ethno-territorial groups of the human population can underlie the epidemiological features of the spread of tuberculosis (TB) and the structure of the genetic component of the susceptibility to the disease. The variability of 62 genetic variants potentially associated with the risk of the development of TB in the Russian population of the city of Tomsk has been studied and the differentiation of various ethno-territorial groups of the world by these markers has been assessed. The studied sample comprised 445 Russian residents of the city of Tomsk without bronchopulmonary pathology. For comparison, the data on the variability of the genetic markers of interest in 26 populations from the 1000 Genomes Project was involved. In the Tomsk population, only the ancestral allele was found for seven of the 58 SNPs studied; the allele frequencies for 36 markers were within the limits of the values seen in other European populations; for 12 SNPs, the observed frequencies were closer to populations with a significant Mongoloid component. By the total of the SNPs, the Tomsk population, despite the geographical distance from the rest of the European populations, did not differ from them (in genetic distances and Gst statistics), although it had some features of the gene pool. Intergroup differentiation of the world populations by these SNPs reflects mainly interracial differences. The greatest differences in the genetic structure between the studied populations were seen for the markers localized in intergenic regions. Statistically significant differences were found when comparing the levels of the average expected heterozygosity between groups of “L4 carrier populations” of mycobacteria and “non-L4” populations, which indicates the impact of the prevalence of different pathogenic lineages of M. tuberculosis on the formation of population specificity of the allelic frequencies.

Nowadays, allergic disorders have become one of the most important social problems in the world. This can be related to the advent of new allergenic agents in the environment, as well as an increasing density of human contact with known allergens, including various proteins. Thus, the development of computer programs designed for the prediction of allergenic properties of proteins becomes one of the urgent tasks of modern bioinformatics. Previously we developed a web accessible Allpred Program (http://www-bionet.sscc.ru/ psd/cgi-bin/programs/Allpred/allpred.cgi) that allows users to assess the allergenicity of proteins by taking into account the characteristics of their spatial structure. In this paper, using AllPred, we predicted the allergenicity of proteins from 462 archaea and bacteria species for which a complete genome was available. The segregation of considered proteins on archaea and bacteria has shown that allergens are predicted more often among archaea than among bacteria. The division of these proteins into groups according to their intracellular localization has revealed that the majority of allergenic proteins were among the secreted proteins. The application of methods for predicting the level of gene expression of microorganisms based on DNA sequence analysis showed a statistically significant relationship between the expression level of the proteins and their allergenicity. This analysis has revealed that potentially allergenic proteins were more common among highly expressed proteins. Sorting microorganisms into the pathogenic and nonpathogenic groups has shown that pathogens can potentially be more allergenic because of a statistically significant greater number of allergens predicted among their proteins.

The genetically mediated ability of the host to provide an adequate immune response to the pathogen plays an important role in the development of tuberculosis infection. Genome-wide association studies performed in different populations revealed the association of a number of chromosomal regions with the development of tuberculosis (TB). At the same time, full characteristics of the factors of genetic susceptibility to the disease remains an unresolved problem, and the associations identified are not always reproduced in studies in other populations. A total of 45 single nucleotide polymorphisms (SNPs) were analyzed in 768 individuals, including 323 tuberculosis patients and 445 healthy individuals. Analysis of associations of tuberculosis with genetic markers was carried out using logistic regression. Permutations were used to account for multiple comparisons. Nominal statistically significant association with tuberculosis was detected for two SNPs, rs10515787 (intronic variant of the EBF1 gene) and rs10956514 (intronic variant of the ASAP1 gene) (p = 0.005 and 0.049, respectively). After the permutation test, only one of the associations was preserved, for rs10515787 (p = 0.003). Thus, in Russians from the city of Tomsk, the association of rs10515787 at the EBF1 gene with the development of tuberculosis was confirmed. However, the results of this study identify rare A allele as a risk factor for the development of TB, while in an earlier study, it was identified as being protective relative to the risk for developing of tuberculosis. The revealed “reverse association” is an interesting fact that requires further investigation.

The variability of potentially important functional polymorphic variants rs2069705 (5'UTR of the IFNG gene), rs17880053 (near 5'UTR of the IFNGR2), rs11126176 (LOC100287361 pseudogene), and rs804271 (near 5'UTR of the NEIL2 gene) was characterized in representatives of four ethnic groups living in the Siberian region. These ethnic groups included three indigenous Mongoloid ethnic groups (Yakuts, the residents of the Republic of Sakha (Yakutia), Tuvinians from the Republic of Tuva, and Buryats from the Republic Buryatia) and the alien Russian population. All of the examined variants were polymorphic. The frequency of the rs2069705 allele C in Russians was 0.5833, while it was in a range from 0.7842 to 0.8967 in representatives of the indigenous populations. The frequency of rs17880053 deletion was 0.8073 in Russians and from 0.4474 to 0.5521 in the indigenous ethnic groups. The frequency of the rs11126176 allele A was equal to 0.5398 in Russians but was recorded with lower frequencies in indigenous ethnic groups (from 0.2722 to 0.4551). The frequency of the rs804271 allele Gwas 0.5215 in Russians and from 0.2527 to 0.4022 indigenous ethnic groups. With respect to the genotype structure, the alien Russian population was considerably distanced from indigenous Mongoloid populations. Specifically, the genetic distance was 0.0742 between Russians and Yakuts, 0.1365 between Russians and Tuvinians, and 0.1433 between Russians and Buryats. Among the Mongoloid indigenous ethnic groups of Siberia, Tuvinians and Yakuts were the most distant from each other (0.0262). The genetic distance was equal to 0.0151 between Yakuts and Buryats and 0.0127 between Buryats and Tuvinians.

BACKGROUND: Genome-wide association studies have identified novel genetic associations for asthma, but without taking into account the role of active tobacco smoking. This study aimed to identify novel genes that interact with ever active tobacco smoking in adult onset asthma.METHODS: We performed a genome-wide interaction analysis in six studies participating in the GABRIEL consortium following two meta-analyses approaches based on 1) the overall interaction effect and 2) the genetic effect in subjects with and without smoking exposure. We performed a discovery meta-analysis including 4,057 subjects of European descent and replicated our findings in an independent cohort (LifeLines Cohort Study), including 12,475 subjects.RESULTS: First approach: 50 SNPs were selected based on an overall interaction effect at pCONCLUSIONS: Using two genome-wide interaction approaches, we identified novel polymorphisms in non-annotated intergenic regions on chromosomes 9 and 12, that showed suggestive evidence for interaction with active tobacco smoking in the onset of adult asthma.

Nowadays, allergic disorders have become one of the most important social problems in the world. This can be related to the advent of new allergenic agents in the environment, as well as an increasing density of human contact with known allergens, including various proteins. Thus, the development of computer programs designed for the prediction of allergenic properties of proteins becomes one of the urgent tasks of mo dern bioinformatics. Previously we developed a web accessible Allpred Program (http://www-bionet.sscc.ru/ psd/cgi-bin/programs/Allpred/allpred.cgi) that allows users to assess the allergenicity of proteins by taking into account the characteristics of their spatial structure. In this paper, using AllPred, we predicted the allergenicity of proteins from 462 archaea and bacteria species for which a complete genome was available. The segregation of considered proteins on archaea and bacteria has shown that allergens are predicted more often among archaea than among bacteria. The division of these proteins into groups according to their intracellular localization has revealed that the majority of allergenic proteins were among the secreted proteins. The application of methods for predicting the level of gene expression of microorganisms based on DNA sequence analysis showed a statistically significant relationship between the expression level of the proteins and their allergenicity. This analysis has revealed that potentially allergenic proteins were more common among highly expressed proteins. Sorting microorganisms into the pathogenic and nonpathogenic groups has shown that pathogens can potentially be more allergenic because of a statistically significant greater number of allergens predicted among their proteins.

The variability of potentially important functional polymorphic variants rs2069705 (5'UTR of the IFNG gene), rs17880053 (near 5'UTR of the IFNGR2), rs11126176 (LOC100287361 pseudogene), and rs804271 (near 5'UTR of the NEIL2 gene) was characterized in representatives of four ethnic groups living in the Siberian region. These ethnic groups included three indigenous Mongoloid ethnic groups (Yakuts, the residents of the Republic of Sakha (Yakutia), Tuvinians from the Republic of Tuva, and Buryats from the Republic Buryatia) and the alien Russian population. All of the examined variants were polymorphic. The frequency of the rs2069705 allele C in Russians was 0.5833, while it was in a range from 0.7842 to 0.8967 in representatives of the indigenous populations. The frequency of rs17880053 deletion was 0.8073 in Russians and from 0.4474 to 0.5521 in the indigenous ethnic groups. The frequency of the rs11126176 allele A was equal to 0.5398 in Russians but was recorded with lower frequencies in indigenous ethnic groups (from 0.2722 to 0.4551). The frequency of the rs804271 allele Gwas 0.5215 in Russians and from 0.2527 to 0.4022 indigenous ethnic groups. With respect to the genotype structure, the alien Russian population was considerably distanced from indigenous Mongoloid populations. Specifically, the genetic distance was 0.0742 between Russians and Yakuts, 0.1365 between Russians and Tuvinians, and 0.1433 between Russians and Buryats. Among the Mongoloid indigenous ethnic groups of Siberia, Tuvinians and Yakuts were the most distant from each other (0.0262). The genetic distance was equal to 0.0151 between Yakuts and Buryats and 0.0127 between Buryats and Tuvinians.

Genome-wide association studies are currently considered as one of the most powerful tools for establishing the genetic basis of complex diseases. A number of such studies have been carried out for allergic diseases; however, in the Russian population, this analysis has not been performed so far. For the first time, we performed a genome-wide association study of allergic diseases in Russian residents of West Siberia. Two new loci associated with childhood bronchial asthma (20q13.12, rs2425656, P = 1.99 × 10−7; 1q32.1, rs3817222, rs12734001, P = 2.18 × 10−7 and 2.79 × 10−7, respectively) as well as one locus associated with allergic rhinitis (2q36.1, rs1597167, P = 3.69 × 10−7) were identified. Genes located in these loci, YWHAB and PPP1R12B for asthma and KCNE4 for allergic rhinitis, are suggested as new candidate genes for these diseases. It was also found that BAT1 (6p21.33), MAGI2 (7q21.11), and ACPL2 (3q23) are probably common (syntropic) genes of allergic disease and atopic sensitization. It was shown that RIT2 (18q12.3) and FSTL4 (5q31.1) genes can be involved in the control of lung function. The results of the study contribute to the body of data on genetic factors of allergy and expand the list of genes underlying these diseases.

The aim of the study was to evaluate the usefulness of the -703С/Т polymorphism in IL-5 gene, Q551R polymorphism in IL-4RA gene, and GSTM1 and GSTТ1 gene polymorphism as biological markers of bronchial asthma (BA) in children with atopic dermatitis (AD). We genotyped children with AD (n = 72; mean age, 9.4 ± 0.28 years), children with AD in combination with BA (n = 68; mean age, 7.5 ± 0.7 years) and control subjects (n = 147; mean age, 9.9 ± 0.42 years). We found the associations between BA and the -703С allele of the interleukin-5 (IL-5) gene (OR = 1.73, p = 0.013) and -703СС / 551RR genotype combination (OR = 3.15; p = 0.015) in children with AD; between the 551RR genotype of the IL-4RA gene and atopy (p < 0.05). -703CT / GSТТ1 0/0 genotype combination was found rarer in children with BA than in controls (OR = 0.15; p = 0.049). Thus, -703С/Т allele of the IL-5 gene and -703СС / 551RR genotype combination were associated with BA and could be used as valuable markers of the disease in children with AD, whereas the Q551R polymorphism in the IL-4RA gene was associated with predisposition to atopic disease and could be used for administration of preventive therapy of allergic disorder in early childhood. The -703CT / GSТТ1 0/0 genotype combination can prevent BA occurrence in children with AD.

Analysis of association of allergic rhinitis with the KCNE4 gene rs12621643 variant was conducted in Russian residents of West Siberia (taking into account comorbidity with bronchial asthma). It was found that, among individuals without bronchial asthma, the frequencies of the KCNE4*G allele and KCNE4*G/G genotype are significantly higher in patients with rhinitis compared to individuals without it. At the same time, no association of rs12621643 with rhinitis was detected in the group of individuals with bronchial asthma. The data obtained indicate the association of the KCNE4 gene variability with allergic rhinitis, although the effect of this gene relative to the development of the disease can be leveled against a background of the manifestation of another atopic disease.

Antioxidant activity (AOA) was measured in 185 inhabitants of the town of Seversk (members of 43 families and unrelated individuals). AOA was defined on the ability of a blood plasma to reduce an output of products, reacting with thiobarbituric acid in the model system «lecithine-Fe2 +-ions». Polymorphism of gastrointestinal glutathione peroxidase (GPX2) gene (two-allelic dinucleotide (TC)n repeat polymorphism) was investigated in 208 individuals. The presence of seasonal changes was revealed and no influences of sex and age on AOA in the considered group were shown. Approximately 50% variance in total AOA was due to the additive effects of genes. No statistical significant association between genetic variability of GPX2 and AOA variation was revealed. Estimation of GPX2 genetic variability contribution to AOA level was 2.53%.

Polymorphism for the GSTT1 and GSTM1 null alleles was analyzed in 69 patients with atopic bronchial asthma (BA) and in 57 healthy individuals from Tomsk. The two samples did not differ in frequencies of genotypes 0/0 and + of either gene or in frequencies of genotype combinations. No association was observed for GST and BA severity. Thus, the GST null alleles proved to be unimportant for BA.

In 3 groups of patients with neoplasms plasma antioxidant activity was measured by the yield of TBA-reactive products generated in lecithin-Fe2+ model system. Patients with laryngeal, tongue, oropharyngeal, oral, and laryngopharyngeal tumors showed lower plasma antioxidant activity compared to patients with breast, lung, and bronchial cancer (p

In 3 groups of patients with neoplasms plasma antioxidant activity was measured by the yield of TBA-reactive products generated in lecithin-Fe(2+) model system. Patients with laryngeal, tongue, oropharyngeal, oral, and laryngopharyngeal tumors showed lower plasma antioxidant activity compared to patients with breast, lung, and bronchial cancer (p0.005). In women with breast cancer plasma antioxidant activity increased with age (p0.05). Possible mechanisms underlying these fluctuations are discussed. It is assumed that plasma antioxidant activity is relatively stable and modulates body resistance to tumor process.