Introduction. Type 2 diabetes (T2D) is a chronic metabolic disorder. The number of diabetic people is increasing. AKT1 is a protein kinase and a participant in the PI3K/AKT/mTOR signaling pathway. The aim of the study was to analyze the association of polymorphic variants rs3803300 and rs2494732 of the AKT1 gene with the risk of developing type 2 diabetes and its complications. Methods. PCR-RFLP analysis was used to study polymorphic variants of two polymorphic loci of the AKT1 gene. DNA samples of 533 patients with T2D and 397 individuals of the control group were used in the work. Results. The association of the rs3803300 locus of the AKT1 gene with the risk of developing T2D, the effect allele T (р=0.02), and the risk genotypes of CT-CC of the rs2494732 locus of the AKT1 gene (р=0.042) were revealed. It was shown that carriers of the CT-CC genotypes of the rs2494732 locus of the AKT1 gene had an increased weight (р=0.026). An association of the rs3803300 locus of the AKT1 gene with the risk of developing diabetic retinopathy (р=0.021), polyneuropathy (р=0.0084), coronary heart disease (р=0.032) and diabetic encephalopathy (р=0.0064) was found. The rs2494732 locus of the AKT1 gene is associated with the development of diabetic nephropathy (р=0.024). Conclusion. The data obtained indicate the prospects of analyzing the PI3K/AKT/mTOR signaling pathway genes for the search for personalized predictors of T2D and its complications.

Type 2 diabetes mellitus (T2DM) is a disease characterized by increased blood glucose, formed as a result of impaired mechanisms of insulin binding to cells. DNA samples of patients with T2DM (N = 535) and healthy individuals (N = 475) were used. We identified the association of lncRNA gene loci LINC02227 rs2149954 (OR = 0.76, P = 0.0083, PFDR = 0.017), LINC00305 rs2850711 (OR = 1.43, P = 0.0017, PFDR = 0.004), and CDKN2B-AS1 rs4977574 (OR = 0.70, P = 0.0001, PFDR = 0.0003) in an additive model with T2DM. The LINC00305 gene locus rs2850711 showed association with fasting glucose level (P = 0.023) and C-peptide level (P = 0.00001); LINC02227 rs2149954 and CDKN2B-AS1 rs4977574 loci showed association with hypertension. MALAT rs619586 gene polymorphism was associated with C-peptide (P = 0.017), LDL (P = 0.012), and total cholesterol levels (P = 0.01). CDKN2B-AS1 rs4977574 gene polymorphism showed association with C-peptide levels (P = 0.027). SNP LINC02227 rs2149954 was associated with obesity (P = 0.0011, PFDR = 0.008). MEG3 rs7158663 gene polymorphism was associated with post infarct cardiosclerosis (P = 0.02). ROC curve analysis showed that the studied loci and variables such as sex, age of subjects, and BMI level included in the construction of the risk calculation model could predict the development of T2DM with a sensitivity of 98.0

Oral Lichen Planus (OLP) is a common chronic inflammatory disease with a high risk of malignization. Early diagnostic tests of erosive and ulcerative form (ECF) of the LP, timely pharmacotherapy are the key to success in the treatment of this form of dermatosis. The cytologic research method is one of the methods by means of which it is possible to obtain the results and adjust the scheme of medication symptomatic treatment in the future. The aim of research is to determine the effect of local treatment on the frequency of cells with nuclear abnormalities in the cytogram of buccal epithelium obtained from the reticular mesh area and from the surface of erosions in patients with the erosive and ulcerative form of the Lichen Planus in the oral cavity mucosa lining. Materials and methods. In the cytogram of buccal epithelium, cytogenetic indicators (micronucleus, tongue-type protrusion, and broken egg-type protrusion), indicators of nucleus destruction (karyopyknosis, karyorrhexis, karyolysis), and indicators of nuclear proliferation (notching) were assessed. Results. The developed method of local treatment of the erosive and ulcerative form of the Lichen Planus contributed to a more significant decrease in the frequency of cells with nuclear proliferation in the form of notches, compared to the group of patients treated according to clinical recommendations (p=0.05), and significantly decreased the frequency of cells with micronuclei (p < 0.01), the frequency of degenerative change of the nucleus at p < 0.05. Both methods of local treatment were effective, however, in clinical subgroups of patients with high titers of Candida spp. detected in the oral microbiota, the effect of local treatment in the form of ozone therapy, contributed to a decrease in the frequency of the cytogenetic indicator in the form of micronucleus protrusion (at p < 0.1), nucleus notching (at p < 0.01), the indicator of completion of nuclear destruction (p < 0.1). Cytologic examination of the buccal epithelium is a non-invasive method that provides clear information about the status of the epithelial cells, in particular their DNA damage, the proliferative potential of basal cells and cell death, which are considered basic principles of cancer alertness.

Ювенильный идиопатический артрит (ЮИА) является тяжелым заболеванием детского и подросткого возраста, и ответ на терапию во многом обусловлен генетическими различиями. Цель работы заключалась в поиске ассоциаций эффективности терапии метотрексатом у больных ЮИА с различными сочетаниями полиморфных аллельных вариантов генов медиаторов иммунного ответа TNF-α rs1800629, IL10 rs1800872 и IL6 rs1800795. В статье представлен анализ распределения диплотипов IL10/IL6 и триплотипов TNF-α/IL10/IL6. В исследовании приняли участие 239 пациентов, получавших базисную терапию с применением метотрексата. С целью генотипирования использовался метод real-time PCR. В подгруппе больных негативной формой ЮИА обнаружена ассоциация полиморфного варианта IL10 -592C>A с отсутствием эффекта на терапию метотрексатом. Установлено, что при наличии одного аллеля IL10*A повышается вероятность отсутствия ответа на терапию, тогда как наличие генотипа *СС повышает шансы ответа. Идентифицированы диплотип (IL10*АA/IL6*GC) и триплотип (TNF-α*GG/IL10*AA/IL6*GC), достоверно чаще встречающиеся в общей группе больных с диагнозом ЮИА среди пациентов с отсутствием ответа на метотрексат. Предполагается, что полученные результаты при дальнейших исследованиях могут быть использованы в качестве фармакогенетических предикторов эффективности терапии у пациентов с ЮИА. Juvenile idiopathic arthritis (JIA) is ineffective in childhood and adolescence and responds to therapy largely due to genetic differences. The aim of the work was to search for associations of methotrexate therapy in JIA patients with the presence of polymorphic allelic variants of the immune response mediator genes TNF-α rs1800629, IL10 rs1800872 and IL6 rs1800795. The article presents an analysis of the distribution of IL10/IL6 diplotypes and TNF-α/IL10/IL6 triplotypes. The experiments involved 239 patients who received basic therapy with the use of methotrexate. For the purpose of genotyping, the real-time PCR method was used. In the subgroup of RF patients with a negative form of JIA, an association of the polymorphic variant IL10 -592C>A with no effect on methotrexate therapy was found. It has been established that the presence of one IL10 *A allele increases the likelihood of a lack of response to therapy, while the presence of the *CC genotype increases the chances of a response. A diplotype (IL10*АA/IL6*GC) and a triplotype (TNF-α*GG/IL10*AA/ IL6*GC) were identified, which are significantly more common in the general group of patients diagnosed with JIA among patients with no response to methotrexate. It is assumed that the results obtained in further studies can be used as pharmacogenetic predictors of the effectiveness of therapy in patients with JIA.

An analysis of polymorphic variants of the serotonin receptor genes HTRD rs674386, HTR1F rs56398417, HTR2A rs6313, HTR3A rs1062613, HTR2C rs6318 and the GABRA2 rs279845 gene in T2D patients living in the Republic of Belarus was carried out. As a result of the study of 6 loci of neurotransmitter genes, protective markers CT and CC genotypes of the rs1062613 locus of the HTR3A gene (OR= 0.73, Pcor_FDR=0.0007) and GC and CC risk genotypes of the rs6318 locus of the HTR2C gene (OR=2.21, Pcor_FDR=0.0045) among women, the CC genotype is also risky for men (R=4.05, Pcor_FDR=0.0045). Analysis of combinations of genotypes and alleles revealed combinations of increased and decreased risk of T2D. The analysis of ROC curves showed that the studied loci and such variables as sex, age of the examined and BMI can be used to assess the prognostic significance of T2D AUC=83.4% (95% CI 83.5-87.4).

Type 2 diabetes mellitus is a multifactorial chronic disease that develops as a result of insulin resistance. One of the causes of insulin resistance is the presence of obesity. The aim of our study was to analyze polymorphic variants of the ghrelin gene GHRL with the development of T2D in the population of the Republic of Bashkortostan. The group of T2D patients included 396 people, the control group included 380 individuals. The study was carried out using the PCR-RFLP method. An increase in the frequency of the rare allele T (Met) of the GHRL rs696217 gene was found in the control group (P=0.004, OR=0.56 (95% CI 0.39-0.81). An analysis was made of quantitative indicators of psychological testing of the level of impulsivity, eating behavior in patients with type 2 diabetes and in controls. Among patients, an association was found with the level of impulsivity (P=0.039), eating disorders according to the EAT-26 questionnaire (P=0.016) and the DEBQ questionnaire for Emotional Eating Behavior in patients (P=0.0062). Analysis of psychological parameters in the control group revealed association with increased body weight of carriers of the Leu/Leu genotype (P=0.0026), BMI level (P=0.02) and violation of the External type of eating behavior (P=0.04). Analysis of the ROC curve shows that the area under the curve (AUC) was 82.4% (95% CI 83.5-87.4) with a sensitivity of 79.0% and a specificity of 75%, indicating a good ability of the selected parameters (the ghrelin gene included in the analysis, as well as age, gender and BMI) to classify individuals for the presence of T2D in the Tatar population. In this study, we assessed the effect of polymorphic variants of the GHRL gene on the development of T2D in the population of Republic of Bashkortostan. The results obtained in our study indicate a protective effect of the locus in the development of T2D in the Republic of Bashkortostan population, which is consistent with the data obtained for Caucasians, but differs from the data typical for Asian populations.

Background. Childhood obesity is topical global healthcare issue. The correlations between variable regions of genes encoding leptin and its receptor, ghrelin and neuropeptide Y, and the risk of obesity development in children have not been confirmed completely. Mechanisms for implementing such correlation via the influence of genes on children’s behavior remain unexplored.Objective. The aim of the study is to examine the correlation between leptin, leptin receptor, ghrelin and neuropeptide Y gene variants and obesity in adolescents and their eating behavior.Methods. The study included children aged from 10 to 18 years with exogenous constitutive obesity and normal body weight. Variants in genes for leptin LEP rs2167270, leptin receptor LEPR rs1137100, ghrelin GHRL rs696217 and rs27647, neuropeptide Y NPY rs16147 were determined. Adolescents’ eating behavior was evaluated via psychometric questionnaires DEBQ (Dutch Eating Behavior Questionnaire) and TFEQ (the Three Factor Eating Questionnaire).Results. Gene variant distribution analysis in 150 obese and 150 normal weight children has revealed correlation with obesity for the variant rs1137100 of the LEPR gene (p = 0.001). Variants rs2167270 of the LEP gene (p = 0.015), rs696217 of the GHRL gene (p = 0.040), and rs16147 of the NPY gene (p = 0.020) were associated with adolescent eating behavior predisposing to obesity.Conclusion. The leptin receptor gene variant rs1137100 is associated with obesity in adolescents, and the variants rs2167270 of the leptin gene, rs696217 of the ghrelin gene, and rs16147 of the neuropeptide Y gene are associated with changes in eating behavior.

Chronic obstructive pulmonary disease (COPD) is a complex chronic inflammatory disease that is characterized by partly reversible airflow limitation, chronic inflammation, fibrosis of small airways, and destruction of lung parenchyma. We aimed to assess the association of the inflammatory gene loci singly and in combinations with COPD in smokers and non-smokers in ethnic Tatar from Russia to evaluate the gene-gene and gene-environment interactions in COPD development. Eleven loci of inflammatory genes, including IL19, IL20, IL24, PPBP, IL4, IL4RA, С5, FAS, FASLG, and TGFb1, were genotyped in 484 smoking COPD patients, 517 healthy smokers, 117 non-smoking COPD patients, and 100 healthy non-smokers. Significant associations with COPD in smokers were identified for IL19 (rs2243193), IL4 (rs2243250), IL4 (rs2070874), and PPBP (rs352010). In non-smokers, associations were established for IL24 (rs291107), IL4 (rs2070874), and PPBP (rs352010). Associations of inflammatory genes loci IL19 (rs2243193), IL4 (rs2070874), TGFb1 (rs1800469), PPBP (rs352010), and FASLG (rs763110) and smoking index were determined. Associations of FAS (rs1800682), FASLG (rs763110), IL4 (rs2243250), IL4RA (rs1805010), and PPBP (rs352010) loci with pulmonary function variables were observed. The results of gene-gene interactions analysis showed distinctive patterns of association of inflammatory gene loci with COPD in groups stratified by smoking status. The combination of A allele of IL19 (rs2243193), C allele of IL4 (rs2243250), and T allele of PPBP (rs352010) was the main component of the majority of protective gene-gene combination associated with COPD in smokers. The highest risk of COPD was conferred by TT genotype of PPBP (rs352010) in combination with A allele of FAS (rs1800682). While in non-smokers, the most commonly featured was IL24 (rs291107) C allele in protective patterns and IL24 (rs291107) T allele in predisposing combinations. The highest risk of COPD in non-smokers was detected in a gene-gene combination consisting of A allele of IL12RB2 (rs3762317) together with G allele of IL12A (rs2243115), C allele of IL4 (rs2070874), and A allele of IL4RA (rs1805010).

Background/objective — The goal of our study was to investigate the role of interaction between the polymorphic loci of immune response mediator genes (TNFA rs1800629, LTA rs909253, IL1B rs16944, IL2-IL21 rs6822844, IL2RA rs2104286, IL6 rs1800795, IL10 rs1800872, MIF rs755622, CTLA4 rs3087243, NFKB1 rs28362491, PTPN22 rs2476601, and PADI4 rs2240336) in the formation of a genetic predisposition to juvenile idiopathic arthritis (JIA). Material and Methods — The study involved 330 JIA patients and 342 volunteers from the Republic of Bashkortostan. Genotyping was conducted via the real-time polymerase chain reaction. The gene-gene interactions were studied using the multifactor dimensionality reduction algorithm. Results — In general analysis, the best model of gene-gene interaction in JIA was a combination of IL1B rs16944 – IL10 rs1800872 – NFKB1 rs28362491 – PADI4 rs2240336 polymorphic loci. However, after gender-based stratification the best results were obtained when examining the combinations of IL6 rs1800795 – PADI4 rs2240336 loci in girls and of IL10 rs1800872 – IL6 rs1800795 – IL2RA rs2104286 loci in boys. Within all of these models, the genotype combinations associated with both augmented and reduced JIA risks were identified (taking into account gender-specific differences). Conclusion — The results of our study implied that an important role in the formation of a predisposition to JIA is played by gene-gene interactions of IL1B rs16944, IL2RA rs2104286, IL6 rs1800795, IL10 rs1800872, NFKB1 rs28362491, and PADI4 rs2240336 polymorphic loci (taking into account gender-specific differences).

Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory lung disease affecting primarily distal respiratory pathways and lung parenchyma. This study aimed to determine possible genetic association of chemokine and chemokine receptor genes polymorphisms with COPD in a Tatar population from Russia. SNPs of CCL20, CCR6, CXCL8, CXCR1, CXCR2, CCL8, CCL23, CCR2, and CX3CL1 genes and their gene–gene interactions were analyzed for association with COPD in cohort of 601 patients and 617 controls. As a result statistically significant associations with COPD in the study group under the biologically plausible assumption of additive genetic model were identified in CCL20 (rs6749704) (P = 0.00001, OR 1.55), CCR6 (rs3093024) (P = 0.0003, OR 0.74), CCL8 (rs3138035) (P = 0.0001, OR 0.67), CX3CL1 (rs170364) (P = 0.023, OR 1.21), CXCL8 (rs4073) (P = 0.007, OR 1.23), CXCR2 (rs2230054) (P = 0.0002, OR 1.32). Following SNPs CCL20 (rs6749704), CX3CL1 (rs170364), CCL8 (rs3138035), CXCL8 (rs4073), CXCR2 (rs2230054) showed statistically significant association with COPD only in smokers. The association of CCR6 (rs3093024) with COPD was confirmed both in smokers and in non-smokers. A relationship between smoking index and CCL20 (rs6749704) (P = 0.04), CCR6 (rs3093024) (P = 0.007), CCL8 (rs3138035) (P = 0.0043), and CX3CL1 (rs170364) (P = 0.04) was revealed. A significant genotype-dependent variation of Forced Vital Capacity was observed for CCL23 (rs854655) (P = 0.04). Forced Expiratory Volume in 1 s / Forced Vital Capacity ratio was affected by CCL23 (rs854655) (P = 0.05) and CXCR2 (rs1126579) (P = 0.02). Using the APSampler algorithm, we obtained nine gene–gene combinations that remained significantly associated with COPD; loci CCR2 (rs1799864) and CCL8 (rs3138035) were involved in the largest number of the combinations. Our results indicate that CCL20 (rs6749704), CCR6 (rs3093024), CCR2 (rs1799864), CCL8 (rs3138035), CXCL8 (rs4073), CXCR1 (rs2234671), CXCR2 (rs2230054), and CX3CL1 (rs170364) polymorphisms are strongly associated with COPD in Tatar population from Russia, alone and in combinations. For the first time combination of the corresponding SNPs were considered and as a result 8 SNP patterns were associated with increased risk of COPD

The role of polymorphic variants of leptin (LEP rs2167270) and leptin receptor (LEPR rs1137100) genes in the development of child obesity and eating behavior was estimated. There was no association with the development of obesity when comparing children's groups with each other. At the same time, the association of LEP (rs2167270) was established according to the following scales of the CEBQ questionnaire: "pleasure of eating, EF", "slowness in eating, SE" and glucose level. For the rs1137100 locus of the LEPR gene, the associations are shown with such anthropometric parameters as birth weight, weight at present, Z-score, and percentile level.

Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory lung disease affecting primarily distal respiratory pathways and lung parenchyma. An abnormal inflammatory response to inhaled harmful particles and tobacco smoke leads to airway remodeling and is thought to be a main mechanism of COPD development. This study aimed to determine possible genetic association of IL12A (rs568408, rs2243115), IL12B (rs3212227), IL13 (rs20541), IL12RB2 (rs3762317) genes polymorphisms with COPD and studied the relationship between selected candidate genes variants with quantitative lung function parameters and smoking index in a Tatar population from Russia. SNPs of IL12A, IL12B, IL13, IL12RB2 genes were analyzed for association with COPD in cohort of 601 patients and 617 controls. SNPs were examined by the real-time polymerase chain reaction (PCR), with the use of TaqMan SNP discrimination assays. As a result statistically significant associations with COPD in the study group under the biologically plausible assumption of additive genetic model were identified in IL12A (rs568408G>A) (P = 0.00001, OR = OR=2.07), IL12A (rs2243115T>G) (P = 0.00001, OR = 2.85), IL13 (rs20541A>G) (P = 0.00001, OR = 1.58). A relationship between smoking index and IL12A (rs568408G>A) (P=0.027), IL12A (rs2243115T>G) (P=0.0038) was revealed. A significant genotype-dependent variation of Forced Vital Capacity was observed for IL12A (rs568408G>A) (P=0.045), IL12A (rs2243115T>G) (P=0.013) and IL13 (rs20541A>G) (P =0.0051). Vital Capacity was affected by IL12A (rs2243115T>G) (P =0.0019). Our data confirm the assumption about the essential role of genes responsible for the synthesis of alpha- and beta-subunits of IL12, structural alpha-helices of IL13 to increased risk of COPD.

For the first time, a study of genetic factors of longevity was conducted in the prevalent populations of 2511 residents of the Republic of Bashkortostan—Russians, Bashkirs, and Tatars. We investigated the polymorphic markers in the genes of the antioxidant defense enzymes— SOD1 (rs2070424), SOD2 (rs4880), and SOD3 (rs1799895). We detected ethnicity-specific patterns of the distribution of genotype frequencies between Bashkir and Russian groups (rs2070424 of the SOD1 gene, P = 0.003), as well as between Tatars and the groups of Russians and Bashkirs (rs4880 of the SOD2 gene, P < 0.001 and 0.035, respectively). We found associations of the polymorphic markers in SOD family genes with age. Among Russians, the chances to attain longevity were higher in the SOD1 *А/А genotype carriers (OR = 1.025, P = 0.001) and lower in those with the SOD1 *А/G (OR = 0.975, Р = 0.001) and SOD2 *А/А (OR = 0.985, Р = 0.002) genotypes. Among Tatars, we observed a decrease in the SOD2 *A/A (OR = 0.989, Р = 0.029) and SOD2 *V/V (OR = 0.985, Р < 0.001) genotype frequencies and an increase in the SOD2 *A/V genotype frequency (OR = 1.023, P < 0.001). The analysis of genotype and/or allelic combinations of the studied polymorphic loci revealed 12 patterns associated with longevity among Tatars. The SOD1 *А and SOD3 *С alleles were present in most of the identified combinations. The SOD2 rs4880 polymorphic marker was indicative of longevity: combinations including the SOD2 *V/V genotype were associated with lower chances of achieving longevity (OR ≤ 0.45, P FDR ≤ 0.0003), and combinations including the SOD2 *A/V genotype were associated with higher chances of achieving longevity (OR ≥ 2.92, P FDR ≤ 1.24 × 10 –6 ).

Долголетие – сложный социально-биологический феномен, при котором человек достигает возраста, значительно превышающего средний популяционный показатель. Вероятность достижения долголетия зависит от совокупности экзогенных и эндогенных факторов. На молекулярно-генетическом уровне характер их взаимодействия определяют гены ферментов метаболизма кислорода и ксенобиотиков, выполняющих функцию защиты организма от токсичных действий внешних агентов. Одним из таких генов является ген параоксоназы 1. Аллели полиморфного маркера rs662 (192Q>R) гена PON1 ассоциированы с активностью фермента и развитием сложно-наследуемых заболеваний, ограничивающих продолжительность жизни. С целью поиска ассоциаций полиморфного маркера rs662 гена PON1 с долголетием в этнической группе башкир проведен сравнительный анализ частот аллелей и генотипов в разных возрастных группах; в общей группе выполнен поиск возрастной динамики частот генотипов с помощью регрессионного анализа. В этнической группе башкир аллели PON1*Q, PON1*R и генотипы PON1*Q/Q, PON1*Q/R, PON1*R/R обнаружены с частотами 69.96, 30.04, 48.7, 42.51, 5.76% соответственно. Полиморфный маркер rs662 гена PON1 оказался ассоциирован с возрастом: шанс достичь долголетия выше у носителей гетерозиготного генотипа PON1*Q/R (55-100 лет, OR=1.022, P=0.043).

Хроническая обструктивная болезнь легких (ХОБЛ) - это многофакторное хроническое воспалительное заболевание респираторной системы. Одной из причин трудностей в идентификации маркеров ХОБЛ является фенотипическая гетерогенность. Цель - идентификация новых молекулярных маркеров патогенетических изменений, связанных с фенотипической гетерогеностью ХОБЛ на основе анализа профиля экспрессии генов вовлеченных в развитие иммунного ответа в мононуклеарных клетках периферической крови и анализа ассоциации полиморфных вариантов новых кандидатных генов с развитием ХОБЛ. Проведен сравнительный анализ профиля экспрессии панели 84 генов, кодирующих цитокины, хемокины в PBMC пациентов с различными фенотипами ХОБЛ: с частыми обострениями N=10 и редкими обострениями N=10 и контрольной группе N=10. Для анализа ассоциации использовали образцы ДНК больных ХОБЛ (N=601) и контроля (N=617), методом ПЦР в реальном времени проведен анализ 56 полиморфных локусов генов JAK/STAT-, NFKB1-сигнального путей, кодирующих белки, вовлеченные в реализацию реакций иммунного ответа и воспаления. Выявлены значимые изменения профиля экспрессии ряда генов в группе больных ХОБЛ с частыми обострениями. Впервые получены данные по вкладу полиморфных локусов генов JAK1, JAK3, STAT3, ICAM1, PECAM1, SAA1, NFKB1, IL17A, CCR2, CCR6, CCL8, CRP, CX3CL1, CXCR2, CXCR1, TNFRSF1A, IL20, IL19, в развитие данного заболевания. Выявлены специфические генетические маркеры развития фенотипа с частыми обострениями: CXCR2, TNFRSF1B, CCR6, TNF, IL1B, IL10, JAK3, PECAM1. Установлена ассоциация полиморфных вариантов генов TNFRSF1B, TNFRSF1A, CCL23, CXCR2, JAK1, NFKB1, PECAM1, ICAM1, STAT1, LTA, CD14, CXCL12, CCL20, ADIPOR1 и CX3CR1 с показателями функции внешнего дыхания. Определена взаимосвязь аллельных вариантов генов: IL17A, JAK1, JAK3, NFKB1, CCL5, CCL11, CCL17, CXCL8, TNFRSF1A, CX3CL1, CCL8, CCR6, CXCR2, IL19, IL20 с индексом курения. Chronic obstructive pulmonary disease (COPD) is a multifactorial heterogeneous chronic inflammatory disease of the respiratory system predominantly affecting the lower respiratory pathways and the lung parenchyma. One of the reason for difficulties in identifying of COPD markers is phenotypic heterogeneity. The goal of the study is the identification of new molecular markers of pathogenetic changes associated with phenotypic heterogeneity of COPD based on the analysis of the expression profile of genes involved in the development of the immune response in peripheral blood mononuclear cells and analysis of the association of polymorphic variants of new candidate genes with COPD. Methods: to identify differential gene expression in COPD we performed expression profiling of 84 cytokines and chemokines genes in peripheral blood samples from COPD (N=10 with frequent exacerbation phenotype, N=10 rare exacerbation phenotype) and N=10 smoking controls. RNA was isolated from PBMCs, and gene expression was assessed using RT2 Profiler PCR Arrays «Human Cytokines & Chemokines PCR Array»» (Qiagen, Valencia, CA, USA). 56 SNPs of JAK / STAT-, NFKB1-signaling pathway and inflammatory response molecules genes were genotyped by the real-time polymerase chain reaction (TaqMan assays) in a case-control study (601 COPD patients and 617 controls). Results. Significant changes were revealed in the expression profile of several genes in “frequent exacerbator» COPD phenotype. The results indicate a down-regulation of inflammatory molecules in “frequent exacerbator» COPD phenotype. For the first time, we indicated the contribution of JAK1, JAK3, STAT3, ICAM1, PECAM1, SAA1, NFKB1, IL17A, CCR2, CCR6, CCL8, CRP, CX3CL1, CXCR2, CXCR1, TNFRSF1A, IL20, IL19 genes polymorphisms to COPD. Specific genetic markers of “frequent exacerbator” COPD phenotype have been identified, which are modifiers of COPD progression, including polymorphic loci of the CXCR2, TNFRSF1B, CCR6, TNF, IL1B, IL10, JAK3, PECAM1 genes. A significant genotype-dependent variation of lung function parameters was observed for CXCR2, JAK1, NFKB1, PECAM1, ICAM1, STAT1, LTA, CD14, CXCL12, CCL20, ADIPOR1 and CX3CR1 genes. The relationship of IL17A, JAK1, JAK3, NFKB1, CCL5, CCL11, CCL17, CXCL8, TNFRSF1A, CX3CL1, CCL8, CCR6, CXCR2, IL19, IL20 genes with smoking pack-years was found.