The article presents the results of a study of the associations of NO synthase and arginase genes in children with bronchial asthma with clinical, laboratory and functional parameters depending on the level of nitrogen oxide in exhaled air (FeNO). We examined 107 children with bronchial asthma, they were divided into 2 groups depending on the level of FeNO. We found a number of associations in the group of patients with an elevated level of FeNO (≥20 ppb): carriage of alleles and genotypes containing short tandem repeats of S (9–11) NOS1(AAT)n gene, with an early debut and severe course of the disease, an increased level of total IgE in blood serum; carriage of alleles and genotypes containing long tandem repeats L (12–16) of the NOS2A(CCTTT) n gene, with a moderate course of the disease, with an increased level of IgE; carriage of the allele *A of the ARGII gene (rs3742879) with a moderate course of the disease; carriage of the *G allele and heterozygous *AG genotype of the ARGII gene (rs3742879) with a decreased level of FEV1/FVC; carriage of L alleles and a combination of the SL and LL genotypes of the NOS1(AAT)n gene with elevated blood eosinophils (eosinophilia); a combination of S/L + L/L genotypes of the NOS1(AAT)n gene with fungal sensitization. The authors established the correlations between disease severity and NOS1(AAT)n; the age of the manifestation of the disease and NOS1(AAT)n; FEV1/FVC and ARGII (rs3742879); feedback between blood eosinophilia and NOS1(AAT)n. The authors also determined a number of associations in the group of patients with low level of FeNO (<20 ppb): carriage of alleles and genotypes containing short tandem repeats of S (9–11) gene NOS1(AAT)n, with fungal sensitization; carriage of alleles and genotypes containing long tandem repeats of L (12–16) gene NOS2A(CCTTT)n, with reduced FEV1 and FEV1/FVC; carriage of the homozygous genotype of *GG gene ARGII(rs3742879) with epidermal sensitization. With a reduced level of FeNO, the study determined a relationship between the severity of bronchial asthma and NOS1(AAT)n; degree of effectiveness of anti-inflammatory basic therapy and NOS1(AAT)n; fungal sensitization and NOS1(AAT)n; feedback between FEV1 and NOS2(CCTTT)n; FEV1/FVC and NOS2(CCTTT)n.
Objective. To analyze the association between NOS1, NOS2, NOS3, ARG1, and ARG2 gene polymorphisms and clinical, laboratory, and functional characteristics of bronchial asthma (BA) in children by evaluating gene-gene interactions. Patients and methods. We have evaluated the associations between the NOSs and ARG genes and gene-gene interactions in 107 children with BA. We performed comparative genetic analysis of associations between polymorphic variants of candidate genes in 107 BA patients and clinical manifestations of the disease, laboratory, and functional parameters. Results. We have found an association between the short (S) allele and SS genotype of the NOS1 (AAT)n gene and early disease onset (<5 years), severe BA, and antiinflammatory targeted therapy (with omalizumab and combination inhaled corticosteroids with long-acting β2-agonists). We have also revealed an association between the short (S) allele and SS genotype of the NOS1 (AAT)n gene, as well as long (L) alleles and LL genotypes of the NOS2A (CCTTT)n gene in BA patients and elevated FeNO levels in the exhaled air. The following association have also been identified: between alleles and genotypes containing long (L) tandem repeats in the NOS2A (CCTTT)n gene and reduced FEV1; between AG genotype of the ARG2 gene (rs3742879), alleles and genotypes containing long tandem repeats (L) of the NOS2А (CCTTT)n gene and reduced FEV1/ FVC; between alleles and genotypes containing long tandem repeats (L), combinations of genotypes SL+LL of the NOS2А (CCTTT)n and impaired patency at the level of the middle bronchi FEF50; between allele G, heterozygous genotype AG of the ARG2 (rs3742879) gene with impaired patency at the level of peripheral bronchi FEF75. Conclusion. Our analysis of gene-gene interactions has demonstrated phenotypic characteristics of BA: early BA onset, severe BA, decreased FEV1 and FEF50, increased NO concentration in exhaled air, and presence of fungal and epidermal sensitization. Key words: children, bronchial asthma, NOS and ARG gene polymorphisms, gene-gene interactions
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