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Background. The problem of atopic march (AM), namely its progression from monoorganic phenotypes of atopic dermatitis (AD), allergic rhinitis/rhinoconjunctivitis (AR/ARC), bronchial asthma (BA) to their multiorgan combinations, is one of the biggest in the modern pediatrics. One of the most important causes for the development of these pathologies are single nucleotide variants (SNV) of the causative genes, orsomucoid-1-like protein 3 (ORMDL3), in particular rs_7216389 ORMDL3. The roles of T- and C-alleles in relation to monoorganic and polyorganic AM phenotypes have not been sufficiently studied. The objective was to study associations of the SNVs rs_7216389 ORMDL3 in the development of different AM phenotypes in children. Materials and methods. There were 293 children recruited into the main group and 105 controls aged 3 to 18 years. Children of the main group had monoorganic and polyorganic phenotypes of AM: AD, AR/ARC, BA, AD+AR/ARC, BA+AR/ARC, AD+AR/ARC+BA. Children of the control group suffered from organic and functional digestive pathology without clinical or paraclinical signs of AM. All children were genotyped for C/C, T/T, C/T variants of SNV rs_7216389 ORMDL3 by allelic discrimination method based on real time polymerase chain reaction with restriction fragment length polymorphism of the buccal swab obtained from each patient. Spearman’s correlation coefficient (rs) was used to determine associations; risks and protective effects were determined using logistic regression analysis by calculating odds ratios (OR) and 95% confidence intervals (CI). The results obtained were significant at p < 0.05 according to the Student’s test. Results. Risks and associations for the monoorganic AR/ARC phenotype: C/C SNV rs_7216389 ­ORMDL3: rs = 0.197, OR = 0.33 (95% CI 0.14–0.78, p < 0.05); T/T SNV rs_7216389 ORMDL3: rs = 0.246, OR = 3.21 (95% CI 1.57–6.59, p < 0.05). For the monoorganic BA phenotype: T/T SNV rs_7216389 ORMDL3: rs = 0.192, CI = 2.97 (95% CI 1.08–8.14, p < 0.05). For the polyorganic AD+AR/ARC phenotype: C/C SNV rs_7216389 ORMDL3: rs = 0.146, OR = 0.42 (95% CI 0.16–1.11, p = 0.05–0.1); T/T SNV rs_7216389 ­ORMDL3: rs = 0.265, OR = 3.64 (95% CI 1.62–8.18, p < 0.05). For the polyorganic BA+AR/ARC phenotype: C/C SNV rs_7216389 ORMDL3: rs = 0.163, OR = 0.42 (95% CI 0.19–0.93, p < 0.05); T/T SNV rs_7216389 ORMDL3: rs = 0.255, OR = 3.34 (95% CI 1.63–6.82, p < 0.01). The C/T SNV rs7216389 ORMDL3 genotype did not reveal significant associations or impact on the development of any AM phenotypes in children. Conclusions. The T-allele SNV rs7216389 ORMDL3 has an inductive impact on the development of AM in children — the homozygous T/T genotype of SNV rs7216389 ORMDL3 is significantly associated with and increases the risk of developing the monoorganic AR/ARC and BA phenotypes, as well as polyorganic AD+AR/ARC and BA+AR/ARC phenotypes. The C-allele SNV rs7216389 ORMDL3 has a protective impact on the development of AM in children — the homozygous genotype C/C of SNV rs7216389 ORMDL3 is significantly associated with and reduces the risk of developing the monoorganic AR/AR phenotype, as well as polyorganic AD+AR/AR and BA+AR/ARC phenotypes.

Background. Atopic disorders (AtD), in particular atopic dermatitis (AD), have a complex genetic basis. There is reliable evidence for associations of thymic stromal lymphopoietin (rs_11466749 TSLP) and orsomucoid-1-like protein 3 (rs_7216389 ORMDL3) gene polymorphisms with the risk of developing mono- and polyorganic phenotypes of AtD in children. The aim of study: to determine associations between SNPs rs_11466749 TSLP and rs_7216389 ORMDL3 and the mono-organic phenotype of AD, to determine the risks of its occurrence with different variants of SNP data related to polyorganic phenotypes of AtD. Materials and methods. Two hundred and ninety-three children of the main group and 105 controls aged 3 to 18 years were recruited in the study. Patients of the main group had established diagnoses of AD, allergic rhinitis/conjunctivitis (AR/AC) and bronchial asthma (BA) in both mono- and multiorganic phenotypes, and the control group did not have AtD and suffered from the gastrointestinal diseases. All patients underwent buccal swab for genotyping the variants A/A, A/G and G/G rs_11466749 TSLP, C/T, C/C and T/T rs_7216389 ORMDL3 using standar­dized kits by the means of real-time polymerase chain reaction with restriction fragment length polymorphism (qPCR). Pearson’s χ2 test, Fisher’s exact test, Bravais-Pearson correlation coefficient (rb) and odds ratio with 95% confidence interval (CI) were used to achieve the stated study aim. The level of statistical significance was taken at p < 0.05, the trend was determined at p < 0.1. Results. The most frequent genotypes among those investigated within the mono-organic phenotype of AD are A/A and A/G rs_11466749 TSLP and C/T rs_7216389 ORMDL3. Genotype T/T rs_7216389 ORMDL3 has a significantly negative low association, and genotype A/G rs_11466749 TSLP — significantly direct medium association with mono-organic AD phenotype relative to polyorganic AD + AR/AC and AD + AR/AC + BA, respectively. There is a significantly reduced risk of developing mono-organic phenotype of AD compared to polyorganic phenotype of AD + AR/AC with the T/T rs_7216389 ORMDL3 genotype — 0.36 (95% CI 0.15–0.88). Related to the full polyorganic phenotype of AD + AR/AC + BA with the A/G rs_11466749 TSLP genotype, the risk of developing the AD phenotype is significantly increased to 5.81 times (95%CI 1.57–21.5). Conclusions. Carriers of A/A rs_11466749 TSLP, C/T and T/T rs_7216389 ­ORMDL3 genotypes have a higher risk of developing mono-organic AD phenotype than digestive disorders. Carriership of the A/G rs_11466749 TSLP genotype significantly increases the risk of the developing the mono-organic AD phenotype compared to the full polyorganic phenotype AD + AR/АC + BA, and of the T/T rs_7216389 ORMDL3 variant has a protective effect for the development of AD compared to the polyorganic phenotype AD + AR/AC.