Clinical and genetic associations of NO-synthase and arginase gene polymorphisms and gene-gene interactions in children with bronchial asthma

Abstract

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