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Asthma is a common severe disease of the respiratory tract, it leads to a significant impairment in the quality of a patient’s life unless effectively treated. Uncontrolled asthma symptoms are a cause of disease progression and development, they lead to an increase in the patient’s disability. The sensitivity to asthma therapy largely depends on the interaction of genetic and epigenetic factors, which account for about 50–60 % of variability of therapeutic response. Beta-2-agonists are some of the major class of bronchodilators used for asthma management. According to published data, allelic variants of the arginase ARG1 and ARG2 genes are associated with a risk of asthma development, spirometry measures and efficacy of bronchodilator therapy. High arginase activity results in a low level of plasma L-arginine and in a decrease in nitric oxide, and, as a result, in an increase in airway inflammation and remodeling. Arginase genetic polymorphisms (rs2781667 of the ARG1 gene, rs17249437, rs3742879, rs7140310 of the ARG2 gene) were studied in 236 children with asthma and 194 unrelated healthy individuals of Russian, Tatar and Bashkir ethnicity from the Republic of Bashkortostan. Association analysis of the studied polymorphisms with asthma development and course, the sensitivity to therapy in patients was carried out. It was found that the rs2781667* C allele of the ARG1 gene is a marker of an increased risk of asthma in Tatars. In Russians, the association of rs17249437* TT and rs3742879* GG genotypes of the ARG2 gene with a decrease in spirometry measures (FEV1, MEF25) was established. In Russians and Tatars receiving glucocorticoid monotherapy or combination therapy, the association of the rs17249437* T allele and rs17249437* TT genotype of the ARG2 gene with a partially controlled and uncontrolled course of asthma was shown.

Bronchial asthma (BA) is a common severe and disabling multifactorial disease. Up to 50–60% of differences in sensitivity to therapy in patients with BA is due to genetic variability. We studied polymorphic variants of four genes involved in the metabolism of glucocorticosteroids in patients with asthma and healthy individuals of Russian, Tatar and Bashkir ethnic origin: rs37973 of the glucocorticoid-induced transcript 1 gene (GLCCI1), rs2305089 of the transcription factor T gene (TBXT), rs10044254 of the F-box and leucine-rich repeat protein gene (FBXL7), rs11123610 of the allantoicase gene (ALLC). It has been established that, in Tatars, the rs37973 G allele of the GLCCI1 gene is a marker of an increased risk of developing BA with an uncontrolled course, while a decrease in spirography is observed in patients with the rs37973 AG and rs37973 GG genotypes of the GLCCI1 gene compared with children with rs37973 AA genotypes. In Bashkirs, a marker of an increased risk of developing the disease is the rs2305089 T allele of the TBXT gene polymorphic variant.

Asthma is a common severe disease of the respiratory tract, it leads to a significant impairment in the quality of a patient's life unless effectively treated. Uncontrolled asthma symptoms are a cause of disease progression and development, they lead to an increase in the patient's disability. The sensitivity to asthma therapy largely depends on the interaction of genetic and epigenetic factors, which account for about 50-60 % of variability of therapeutic response. Beta-2-agonists are some of the major class of bronchodilators used for asthma management. According to published data, allelic variants of the arginase ARG1 and ARG2 genes are associated with a risk of asthma development, spirometry measures and efficacy of bronchodilator therapy. High arginase activity results in a low level of plasma L-arginine and in a decrease in nitric oxide, and, as a result, in an increase in airway inflammation and remodeling. Arginase genetic polymorphisms (rs2781667 of the ARG1 gene, rs17249437, rs3742879, rs7140310 of the ARG2 gene) were studied in 236 children with asthma and 194 unrelated healthy individuals of Russian, Tatar and Bashkir ethnicity from the Republic of Bashkortostan. Association analysis of the studied polymorphisms with asthma development and course, the sensitivity to therapy in patients was carried out. It was found that the rs2781667*C allele of the ARG1 gene is a marker of an increased risk of asthma in Tatars. In Russians, the association of rs17249437*TT and rs3742879*GG genotypes of the ARG2 gene with a decrease in spirometry measures (FEV1, MEF25) was established. In Russians and Tatars receiving glucocorticoid monotherapy or combination therapy, the association of the rs17249437*T allele and rs17249437*TT genotype of the ARG2 gene with a partially controlled and uncontrolled course of asthma was shown.Бронхиальная астма (БА) – широко распространенное тяжелое заболевание дыхательных путей, которое при недостаточно эффективном лечении приводит к значительному ухудшению качества жизни пациентов. Отсутствие контроля над симптомами БА ведет к быстрому прогрессированию, утя- желению заболевания и инвалидизации пациентов. Чувствительность к лекарственной терапии БА во многом зависит от взаимодействия генетических и эпигенетических факторов, которые на 50–60 % опре- деляют вариабельность терапевтического ответа пациентов. Одной из основных групп препаратов, используемых для лечения БА, являются бета-2-агонисты, оказывающие значительное бронходилатирующее действие. По литературным данным, аллельные варианты генов аргиназ ARG1 и ARG2 ассоциированы с риском развития БА, показателями спирографии и эффективностью терапии бронходилататорами. Повы- шенная экспрессия генов аргиназ ведет к снижению биодоступности L-аргинина и уровня оксида азота в организме и, как следствие, к увеличению степени воспаления и ремоделирования дыхательных путей. Выполнено исследование полиморфных вариантов генов аргиназ (rs2781667 гена ARG1 и rs17249437, rs3742879, rs7140310 гена ARG2) у 236 детей, больных БА, а также у 194 неродственных здоровых индиви- дов русской, татарской и башкирской этнической принадлежности, проживающих на территории Респу- блики Башкортостан. Проведен поиск ассоциаций изученных полиморфных вариантов с развитием, тече- нием БА и чувствительностью к терапии у пациентов с БА. Установлено, что аллель rs2781667*С гена ARG1 является маркером повышенного риска развития БА у татар. В группе русских пациентов с БА генотипы rs17249437*TT и rs3742879*GG гена ARG2 ассоциированы со снижением показателей спирографии (ОФВ1, МОС25). У русских и татар, находящихся на монотерапии ингаляционными глюкокортикостероидами или на комбинированной терапии, показана ассоциация аллеля rs17249437*Т и генотипа rs17249437*TT гена ARG2 с частично контролируемым и неконтролируемым течением астмы.

Background. To identify the set of possible predictors of atopic dermatitis forming in children. Methods. There were 440 children aged from 0 to 18 years old (315 patients with atopic dermatitis, 125 - children of the monitoring group) under investigation. Mathematical models used logistic regression method were developed. Results. On the basis of the obtained data the logistic regression equation was selected, including 16 predictors, statistical significance of which was within 5% of the Wald statistics. Conclusion. Practical application of the devised formula will help to identify children with high risk to develop atopic dermatitis.

The article presents modern data on gasdermin B (GSDMB) gene involved in the control of cell cycle, apoptosis, terminal differentiation of epithelial cells and maintain barrier function of the skin.

Atopic dermatitis is a common chronic inflammatory skin disease and depends on the interaction between environmental factors and genetic predisposition. A considerable role in allergic disorders is played by polymorphisms of the genes of pattern recognition receptors (PRRs), which recognize conserved standard molecular structures (patterns) unique to large pathogen groups. Polymorphisms of several PRR genes, including the genes of Toll-like receptors (TLR1, TLR2, TLR4, TLR5, TLR6, TLR9, and TLR10), NOD-like receptors (NOD1 and NOD2), and a lipopolysaccharide receptor (CD14) along with C11orf30 and LRRC32 from chromosome 11q13.5, were studied in atopic dermatitis patients and control subjects from Bashkortostan. TLR1 (rs5743571 and rs5743604), TLR6 (rs5743794), and TLR10 (rs11466617) polymorphisms were associated with atopic dermatitis. The results supported the idea that innate immunity and polymorphisms of the TLR2-family genes play a substantial role in atopic dermatitis.

Bronchial asthma is a chronic inflammatory respiratory disease that is caused by the complex interaction of environmental influences and genetic susceptibility. The first genome-wide association study of bronchial asthma discovered a significant association between SNPs within 17q12-21 genomic region and childhood bronchial asthma in individuals of European descent. Association with this genomic region was then replicated in a number of independent samples of European and Asian descent. Here we report results of the first genome-wide association study of bronchial asthma in the Volga-Ural region of Russia. The present study includes 358 unrelated patients with physician-diagnosed bronchial asthma and 369 disease-free control subjects of different ethnic origin (Russians, Tatars and Bashkirs). Genotyping of DNA samples was carried out using the Illumina Human610 quad array as a part of GABRIEL project (contract from the EC No LSHB-CT-2006-018996). After QC filtering procedures, a final set of 550915 SNPs genotyped in 330 cases and 348 controls was tested for association with bronchial asthma. Five markers on chromosome 17q12-21 showed statistically significant association with bronchial asthma (p < or = 4.79 x 10(-7)). SNP rs7216389 with the strongest evidence for association (p = 1.01 x 10(-7)) is located within the first intron of the GSDMB gene. Evidence for association was stronger with childhood-onset asthma (p = 1.97 x 10(-6) for SNP rs7216389) compared to late-onset asthma (p = 1.8 x 10(-4) for SNP rs7216389). Our replication study using three SNPs within GSDMB gene confirmed association with only childhood-onset asthma. In summary, these results suggest an important role for genetic variants within 17q12-q21 region in the development of bronchial asthma in the Volga-Ural region of Russia.

Biotransformation enzymes involved in the metabolism of exogenous and endogenous compounds efficiently protect the organism from harmful environmental factors. Decreased activity or insufficient synthesis of biotransformation enzymes due to genetic polymorphism is a risk factor for various complex diseases, including atopy. Allele-specific hybridization on a biochip was used to evaluate the frequencies of xenobiotic metabolism gene polymorphisms in children with bronchial asthma and/or allergic rhinitis and in healthy donors, all residents of the Republic of Bashkortostan of Russian descent. Polymorphisms of CYP1A1, GSTT1, GSTM1, NAT2, MTHFR, CYP2C9, and CYP2C19 were not associated with atopic diseases in children. The genotype CYP2D6*1934G/G and the allele CYP2D6*1934G were associated with an increased risk of allergic rhinitis in boys.

Bronchial asthma is a chronic inflammatory respiratory disease that is caused by the complex interaction of environmental influences and genetic susceptibility. The first genome-wide association study of bronchial asthma discovered a significant association between SNPs within 17q12-21 genomic region and childhood bronchial asthma in individuals of European descent. Association with this genomic region was then replicated in a number of independent samples of European and Asian descent. Here we report results of the first genome-wide association study of bronchial asthma in the Volga-Ural region of Russia. The present study includes 358 unrelated patients with physician-diagnosed bronchial asthma and 369 disease-free control subjects of different ethnic origin (Russians, Tatars and Bashkirs). Genotyping of DNA samples was carried out using the Illumina Human610 quad array as a part of GABRIEL project (contract from the EC No LSHB-CT-2006-018996). After QC filtering procedures, a final set of 550915 SNPs genotyped in 330 cases and 348 controls was tested for association with bronchial asthma. Five markers on chromosome 17q12-21 showed statistically significant association with bronchial asthma (por = 4.79 x 10(-7)). SNP rs7216389 with the strongest evidence for association (p = 1.01 x 10(-7)) is located within the first intron of the GSDMB gene. Evidence for association was stronger with childhood-onset asthma (p = 1.97 x 10(-6) for SNP rs7216389) compared to late-onset asthma (p = 1.8 x 10(-4) for SNP rs7216389). Our replication study using three SNPs within GSDMB gene confirmed association with only childhood-onset asthma. In summary, these results suggest an important role for genetic variants within 17q12-q21 region in the development of bronchial asthma in the Volga-Ural region of Russia.

Enzymes of biotransformation system involved in the metabolism of exogenous and endogenous compounds are effective mechanism of protection from negative environmental factors. Decreasing activity or insufficient synthesis of biotransformation system enzymes caused by genetic polymorphism form the risk of various complex diseases, including atopic. Using allele-specific hybridization on the biochip the frequencies of xenobiotic-metabolizing gene polymorphisms in Russian children with bronchial asthma, allergic rhinitisand healthy donors from the Republic of Bashkortostan have been determined. The analysis of polymorphisms in CYP1A1, GSTT1, GSTM1, NAT2, MTHFR, CYP2C9 and CYP2C19 genes didn't reveal any association with atopic diseases. The frequencies of CYP2D6*1934G/G genotype and CYP2D6*1934G allele were significantly higher among boys with rhinitis symptoms than in control group.

The purpose of this study was to investigate the possible roles of the genes functioning in xenobiotic metabolism and antioxidant pathways in the development of severe chronic lung disease in children. Polymorphisms in the genes encoding CYP1A1, CYP2E1, EPHX1, GSTM1, GSTT1, and GSTP1 were investigated in cases of Tatar children with chronic bronchitis (n=129) and relapsing pneumonia (n=50) and in cases of ethnically matched healthy individuals (n=227) living in the city of Ufa, the Republic of Bashkortostan (South Ural region of Russia), by polymerase chain reaction-restriction fragment length polymorphism (PCR-RLFP) method. The frequency of the *2C allele of the CYP1A1 gene was significantly higher in patients than in the healthy control group (chi2=15.02, P=0.0007, Pcor=0.0021). This allele was associated with a higher risk of chronic bronchitis in children (OR 4.14, 95% CI 1.83-9.53; Pcor=0.0024). Similar results were obtained in cases of patients with relapsing pneumonia (OR 3.86, 95% CI 1.34-10.95; Pcor=0.027 for the *2C allele of the CYP1A1 gene). The frequency of the *5B allele of the CYP2E1 gene was higher in the relapsing pneumonia patients (7.0 vs 1.98% in the control group; chi2=5.68, P=0.018, Pcor=0.054; OR 3.72, 95% CI 1.21-11.24). The increase in the GSTT1 gene deletion was significant only in cases of chronic bronchitis (39.53 compared to 21.15% in the control group; chi2=12.96, P=0.001, Pcor=0.003; OR 2.44, 95% CI 1.48-4.04). Our results show that the presence of the GSTM1 gene deletion is unfavorable for the development of chronic lung disease in females (chi2=9.57; P=0.0029, Pcor=0.0116) and was associated with increased risk (OR 2.44, 95% CI 1.36-4.38). The distribution of EPHX1 and GSTP1 gene genotypes was similar in the control and patient groups. Our findings indicate that the polymorphisms of the CYP1A1, CYP2E1, and GSTT1 genes probably play a substantial part in susceptibility to severe airway and lung injury in cases of children with chronic bronchitis and relapsing pneumonia.

The volume and type of treatment and prophylactic care rendered on an outpatient basis to children during a year is assessed based on a sampling from files of 2083 disabled children living in a large industrial city Ufa. In contrast to the entire population of children, each disabled child receives more visits from doctors at home and visits the health center more often. The majority of visits to the health center are for treatment and diagnosis and for consultations. Local doctors are visited mainly for prevention. The activity of local nurses responsible for follow-up of disabled children is low.

The article presents data on influence of technogenic environmental pollution and parents' occupational hazards on sex-matched physical development of preschoolers, their endocrine balance and antioxidant system. The identified features of physical development, endocrine state and antioxidant system prove higher sensitivity of girls to chemical hazards. Significance of the studied parameters necessitate their use in biologic and ecologic monitoring.