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Papers by A. Rudko

Russian Journal of Allergy

This review summarizes the results of pharmacogenetic studies of determination response to drugs ... more This review summarizes the results of pharmacogenetic studies of determination response to drugs used for the treatment of bronchial asthma. Pharmacogenetic information will enable the use of a personalized approach to the asthma management, which will adjust the therapy technology and increase the possibility of achieving disease control.

Bulletin of Siberian Medicine

Crohn’s disease (CD) and tuberculosis (TB) share several mechanisms of pathogenesis, and this sug... more Crohn’s disease (CD) and tuberculosis (TB) share several mechanisms of pathogenesis, and this suggests they also have common genetic susceptibility factors. To test this hypothesis, we performed the analysis of association between TB and polymorphisms of genes associated with CD, according to the results of genome-wide association studies, in Russians from Tomsk and indigenous people from Tuva. For the first time, The rs2872507 (ORMDL3), rs3810936 (TNFSF15), rs10192702 (ATG16L1), rs9286879 (1q24.3), rs10507523 (13q14.11) polymorphisms were found to be associated with TB in Russians. The rs1407308 (TNFSF15) and rs1736135 (21q21.1) were associated with the disease in Tuvinians. The associations found are likely due to the functional role of the relevant proteins and their pathogenetic influence on the immune reaction underlying tuberculosis infection. Overall, the study of polymorphisms associated with CD allowed us to identify new candidate genes for TB.

The articles presents results of associative study of pulmonary tuberculosis and 17 genes with th... more The articles presents results of associative study of pulmonary tuberculosis and 17 genes with the wide competence field, which products are informative in relations to development of multi-factorial diseases of various etiology. The biggest number of associations was found out to the gene of NOS3 (in particular with rs1799983) – they were registered as associations with pulmonary tuberculosis in general (p = 0.003), and with its clinical forms (p = 0.006), tissue destruction level (p = 0.029), endophenotypes (0.002 ≤ p ≤ 0.033 for various clinical manifestations). The following combinations of genotypes of VNTR/rs1799983 are generally associated with studied pathology (gene of NOS3), rs3746190/rs11575926 (gene of IL12RB1), rs909253/rs1800629 (gene LTA/TNF). Moreover the following polymorphous variants of genes are associated with qualitative and quantitative signs of pulmonary tuberculosis: TNF, LTA, TNFRSF1B, IL12RB1, IFNGR2, ADRB2, IL4R, GNB3. The associative study of genes of GN...

Tuberkulez i Bolezni Lëgkih, 2015

-Polymorphisms of the tuberculosis (TB) susceptibility genes SLC11A1, VDR, IL12B, IL1B , and IL1R... more -Polymorphisms of the tuberculosis (TB) susceptibility genes SLC11A1, VDR, IL12B, IL1B , and IL1RN were studied, for the first time in Russia, in Tuvinians from the Tyva Republic and ethnic Russians from Tomsk. Compared with Russians, Tuvinians had significantly higher frequencies of potentially pathological alleles SLC11A1 *543N (0.139 vs. 0.043, P = 4.6 · 10 -5 ), IL12B *1188C (0.378 vs. 0.174, P = 1.1 · 10 -8 ), VDR *b (0.825 vs. 0.532, P = 3.2 · 10 -16 ), IL1B *(+3953A1) (0.865 vs. 0.806, P = 0.035), and IL1RN *A1 (0.849 vs. 0.786, P = 0.030). However, none of the alleles was associated with TB in Tuvinians. Compared with healthy subjects, Russian patients with TB had higher frequencies of alleles IL1RN *A2 (0.258 vs. 0.186, P = 0.024), SLC11A1 *274T (0.251 vs. 0.164, P = 0.009), IL12B *1188C (0.240 vs. 0.174, P = 0.044), and IL1B *(+3953A2) (0.259 vs. 0.194, P = 0.044). The structure of linkage disequilibrium in pairs of alleles differed between Tuvinians and Russians. In total...

и GSTM1 (GST-µ1) и NOS3 (полиморфизм VNTR4) у шахтёров, больных хроническим пылевым бронхитом,... more 1) и GSTM1 (GST-µ1) и NOS3 (полиморфизм VNTR4) у шахтёров, больных хроническим пылевым бронхитом, и у лиц без этой профессиональной патологии. Показано, что обладатели генотипов EsD1-2, AсP bb наиболее подвержены развитию хронического пылевого бронхита. Эндогенными факторами резистентности к этому заболеванию являются генотипы GC 1-1, EsD 1-1, AсP bc.

Tuberculosis is a significant medical and social problem due to the high prevalence, high degree ... more Tuberculosis is a significant medical and social problem due to the high prevalence, high degree of disability and mortality. Latent tuberculosis infection (LTBI) develops in the majority of cases after infection of M. tuberculosis . It is almost impossible to estimate exactly the prevalence LTBI (according to WHO - it is about 30% of population), because this condition diagnoses only in children and HIV-infected people. The aim of our study was to determine the genes associated with LTBI. 62 SNPs were analyzed in 70 LTBI patients and 445 healthy donors. Associations with LTBI were identified for three markers: rs2505675 (pperm = 0.020), rs958617 (pperm = 0.019), rs6676375 (pperm = 0.021). Interlocus combinations of genotypes characterizing possible intergenic (epistatic) interactions were revealed for the risk assessment of LTBI by MB-MDR. Four two-locus statistically significant models (p Туберкулез является значимой медико-социальной проблемой в связи с широкой распространенность...

Контактная информация:Кондратьева Елена Ивановна, доктор медицинских наук, профессор,заведующий к... more Контактная информация:Кондратьева Елена Ивановна, доктор медицинских наук, профессор,заведующий кафедрой педиатрии ФПК и ППС ГОУ ВПО Сибирскогогосударственного медицинскогоуниверситетаАдрес: 634050, Томск, Московский тракт, д.4, тел. (3822) 531012 Статья поступила 03.07.2007 г.,принята к печати 15.10.2007 г.

Iranian Journal of Medical Sciences, 2019

Background: Tuberculosis (TB) is one of the most significant health-care problems worldwide. The ... more Background: Tuberculosis (TB) is one of the most significant health-care problems worldwide. The host’s genetics play an important role in the development of TB in humans. The disease progresses through several stages, each of which can be under the control of different genes. The precise genes influencing the different stages of the disease are not yet identified. The aim of the current study was to determine the associations between primary and secondary TB and the polymorphisms of novel candidate genes for TB susceptibility, namely CD79A, HCST, CXCR4, CD4, CD80, CP, PACRG, and CD69. Methods: A total of 357 patients with TB (130 cases with primary TB and 227 cases with secondary TB) from the Siberian region of Russia as well as 445 healthy controls were studied. The study was performed at the Research Institute of Medical Genetics, Tomsk NRMC, Tomsk, Russia, between July 2015 and November 2016. Genotyping was carried out using MALDI-TOF mass spectrometry and PCR-RFLP. The associat...

Russian Journal of Genetics, 2018

⎯Specificity of the structure of gene pools of different ethno-territorial groups of the human po... more ⎯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 G st 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.

Genes and Environment, 2017

If citing, it is advised that you check and use the publisher's definitive version for pagination... more If citing, it is advised that you check and use the publisher's definitive version for pagination, volume/issue, and date of publication details. And where the final published version is provided on the Research Portal, if citing you are again advised to check the publisher's website for any subsequent corrections.

Russian Journal of Genetics, 2018

⎯The genetically mediated ability of the host to provide an adequate immune response to the patho... more ⎯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.

Meta Gene, 2017

Abstract Tuberculosis is a global healthcare challenge. Host genetic factors were proven to modif... more Abstract Tuberculosis is a global healthcare challenge. Host genetic factors were proven to modify risk of the disease. Genome-wide association studies revealed a number of loci associated with TB in different populations. However, no systematic analysis of genetic bases of susceptibility to different clinical stages, such as primary TB and reactivation, was carried out. We set out to validate the results of GWASs in Russians of West Siberia with a consideration of primary and secondary TB. We chose 45 SNP from five large GWASs and genotyped 445 healthy individuals and 323 TB patients including 74 with primary TB and 249 with reactivation. We found that the rs7821565 and rs40363 SNPs were associated with primary TB in Russians (p = 0.019 and 1.4e − 3, respectively), while rs10515787 and rs2837857 were associated with secondary TB (p = 1.2e − 3 and 0.039, respectively). The results suggest genetic basis of primary and secondary TB differs.

Infection, Genetics and Evolution, 2016

Tuberculosis (TB) is a common infectious disease caused by M. tuberculosis. The risk of the disea... more Tuberculosis (TB) is a common infectious disease caused by M. tuberculosis. The risk of the disease is dependent on complex interactions between host genetics and environmental factors. Accumulated genomic data, along with novel methodological approaches such as associative networks, facilitate studies into the inherited basis of TB. In the current study, we carried out the reconstruction and analysis of an associative network representing molecular interactions between proteins and genes associated with TB. The network predominantly comprises of well-studied key proteins and genes which are able to govern the immune response against M. tuberculosis. However, this approach also allowed us to reveal 12 proteins encoded by genes, the polymorphisms of which have never been studied in relation to M. tuberculosis infection. These proteins include surface antigens (CD4, CD69, CD79, CD80, MUC16) and other important components of the immune response, inflammation, pathogen recognition, cell migration and activation (HCST, ADA, CP, SPP1, CXCR4, AGER, PACRG). Thus, the associative network approach enables the discovery of new candidate genes for TB susceptibility.

European Respiratory Journal, 2016

Tuberculosis (TB) is infection disease caused by Mycobacterium tuberculosis ; however, genetic ba... more Tuberculosis (TB) is infection disease caused by Mycobacterium tuberculosis ; however, genetic background of individuals shows influences on susceptibility to disease. Our goal is to establish the novel genes associated with TB using bioinformatics approach. We carried out the reconstruction of associative network representing links between proteins and genes involved in the development of TB. The associative network of TB was reconstructed using the ANDSystem software. For analysis of genes associated with TB from associative network we used genome databases (Ensembl, NCBI, HuGE Navigator). We used RegulomeDB to predict whether a variant affects transcription factor binding and gene expression. In the associative network, well studied proteins and genes with a decisive importance in the efficiency of the human immune response against a pathogen predominated. This approach identified 12 novel genes ( ADA, CP, CD80, CXCR4, HCST, MUC16, CD69, PACRG, AGER, SPP1, CD4, CD79A ) encoding for the proteins in the associative network polymorphisms of which has not been studied regarding the development of TB. The 328 promoter variants of novel TB genes have in varying degrees regulatory effect in accordance with the score assigned to the RegulomeDB. In addition 34 of them have maximum score assuming the maximum possible effect on gene expression. In this work, we identified 12 novel candidate for TB genes. In these genes we found 34 SNPs with possible effect on gene expression. Their validation may help to improve of knowledge of pathogenetic mechanisms of TB and solve the global problem of this disease treatment. This work is supported by the Russian Science Foundation under grant (15-15-00074).

Asian Pacific Journal of Tropical Disease, 2016

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Molekuliarnaia biologiia

The 469 + 14 G/C (INT4), 1465 - 85 G/A, and C274T polymorphisms of NRAMP1 and the A/C polymorphis... more The 469 + 14 G/C (INT4), 1465 - 85 G/A, and C274T polymorphisms of NRAMP1 and the A/C polymorphism of IL12 3'-UTR were analyzed in ethnic Russians with (N = 58) or without (N = 127) tuberculosis (TB) from Tomsk. On evidence of allele and genotype frequencies, none of the polymorphisms was associated with TB. In the healthy controls, the three NRAMP1 polymorphisms were in linkage disequilibrium with each other (P < 0.001) but not with the IL12 polymorphism. Still the four polymorphisms are potentially informative as concerns their association with TB.

PLoS Pathogens, 2010

Leprosy is an infectious disease caused by the obligate intracellular pathogen Mycobacterium lepr... more Leprosy is an infectious disease caused by the obligate intracellular pathogen Mycobacterium leprae and remains endemic in many parts of the world. Despite several major studies on susceptibility to leprosy, few genomic loci have been replicated independently. We have conducted an association analysis of more than 1,500 individuals from different case-control and family studies, and observed consistent associations between genetic variants in both TLR1 and the HLA-DRB1/DQA1 regions with susceptibility to leprosy (TLR1 I602S, case-control P = 5.7610 28 , OR = 0.31, 95% CI = 0.20-0.48, and HLA-DQA1 rs1071630, case-control P = 4.9610 214 , OR = 0.43, 95% CI = 0.35-0.54). The effect sizes of these associations suggest that TLR1 and HLA-DRB1/DQA1 are major susceptibility genes in susceptibility to leprosy. Further population differentiation analysis shows that the TLR1 locus is extremely differentiated. The protective dysfunctional 602S allele is rare in Africa but expands to become the dominant allele among individuals of European descent. This supports the hypothesis that this locus may be under selection from mycobacteria or other pathogens that are recognized by TLR1 and its co-receptors. These observations provide insight into the long standing host-pathogen relationship between human and mycobacteria and highlight the key role of the TLR pathway in infectious diseases.

Molecular Biology, 2006

Polymorphisms of the tuberculosis (TB) susceptibility genes SLC11A1, VDR, IL12B, IL1B , and IL1RN... more Polymorphisms of the tuberculosis (TB) susceptibility genes SLC11A1, VDR, IL12B, IL1B , and IL1RN were studied, for the first time in Russia, in Tuvinians from the Tyva Republic and ethnic Russians from Tomsk. Compared with Russians, Tuvinians had significantly higher frequencies of potentially pathological alleles SLC11A1 *543N (0.139 vs. 0.043, P = 4.6 • 10-5), IL12B *1188C (0.378 vs. 0.174, P = 1.1 • 10-8), VDR *b (0.825 vs. 0.532, P = 3.2 • 10-16), IL1B *(+3953A1) (0.865 vs. 0.806, P = 0.035), and IL1RN *A1 (0.849 vs. 0.786, P = 0.030). However, none of the alleles was associated with TB in Tuvinians. Compared with healthy subjects, Russian patients with TB had higher frequencies of alleles IL1RN *A2 (0.258 vs. 0.186, P = 0.024), SLC11A1 *274T (0.251 vs. 0.164, P = 0.009), IL12B *1188C (0.240 vs. 0.174, P = 0.044), and IL1B *(+3953A2) (0.259 vs. 0.194, P = 0.044). The structure of linkage disequilibrium in pairs of alleles differed between Tuvinians and Russians. In total, the results suggest ethnic specificity of the distribution and pathogenetic significance of the alleles of the TB susceptibility genes.

Russian Journal of Allergy

Bulletin of Siberian Medicine

Tuberkulez i Bolezni Lëgkih, 2015

и GSTM1 (GST-µ1) и NOS3 (полиморфизм VNTR4) у шахтёров, больных хроническим пылевым бронхитом,... more 1) и GSTM1 (GST-µ1) и NOS3 (полиморфизм VNTR4) у шахтёров, больных хроническим пылевым бронхитом, и у лиц без этой профессиональной патологии. Показано, что обладатели генотипов EsD1-2, AсP bb наиболее подвержены развитию хронического пылевого бронхита. Эндогенными факторами резистентности к этому заболеванию являются генотипы GC 1-1, EsD 1-1, AсP bc.

Iranian Journal of Medical Sciences, 2019

Russian Journal of Genetics, 2018

Genes and Environment, 2017

Russian Journal of Genetics, 2018

Meta Gene, 2017

Infection, Genetics and Evolution, 2016

European Respiratory Journal, 2016

Asian Pacific Journal of Tropical Disease, 2016

Molekuliarnaia biologiia

PLoS Pathogens, 2010

Molecular Biology, 2006