Variants of the single nucleotide polymorphisms of thymic stromal lymphopoietin and orsomucoid-1-like protein 3 as predictors of the mono- and polyorganic clinical phenotypes of atopic disorders in children
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 mo...
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Format: | Article |
Language: | English |
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Zaslavsky O.Yu.
2022-10-01
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Series: | Zdorovʹe Rebenka |
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Online Access: | https://childshealth.zaslavsky.com.ua/index.php/journal/article/view/1529 |
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author | V. Dytiatkovskyi |
author_facet | V. Dytiatkovskyi |
author_sort | V. Dytiatkovskyi |
collection | DOAJ |
description | 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. |
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spelling | doaj.art-deaaf15531f3474fad6cc35a947c98152023-06-04T15:42:08ZengZaslavsky O.Yu.Zdorovʹe Rebenka2224-05512307-11682022-10-0117627628110.22141/2224-0551.17.6.2022.15291529Variants of the single nucleotide polymorphisms of thymic stromal lymphopoietin and orsomucoid-1-like protein 3 as predictors of the mono- and polyorganic clinical phenotypes of atopic disorders in childrenV. Dytiatkovskyi0https://orcid.org/0000-0002-8508-5562Dnipro State Medical University, Dnipro, UkraineBackground. 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.https://childshealth.zaslavsky.com.ua/index.php/journal/article/view/1529single-nucleotide polymorphismsmono-organic phenotypespolyorganic phenotypesatopic dermatitischildren |
spellingShingle | V. Dytiatkovskyi Variants of the single nucleotide polymorphisms of thymic stromal lymphopoietin and orsomucoid-1-like protein 3 as predictors of the mono- and polyorganic clinical phenotypes of atopic disorders in children Zdorovʹe Rebenka single-nucleotide polymorphisms mono-organic phenotypes polyorganic phenotypes atopic dermatitis children |
title | Variants of the single nucleotide polymorphisms of thymic stromal lymphopoietin and orsomucoid-1-like protein 3 as predictors of the mono- and polyorganic clinical phenotypes of atopic disorders in children |
title_full | Variants of the single nucleotide polymorphisms of thymic stromal lymphopoietin and orsomucoid-1-like protein 3 as predictors of the mono- and polyorganic clinical phenotypes of atopic disorders in children |
title_fullStr | Variants of the single nucleotide polymorphisms of thymic stromal lymphopoietin and orsomucoid-1-like protein 3 as predictors of the mono- and polyorganic clinical phenotypes of atopic disorders in children |
title_full_unstemmed | Variants of the single nucleotide polymorphisms of thymic stromal lymphopoietin and orsomucoid-1-like protein 3 as predictors of the mono- and polyorganic clinical phenotypes of atopic disorders in children |
title_short | Variants of the single nucleotide polymorphisms of thymic stromal lymphopoietin and orsomucoid-1-like protein 3 as predictors of the mono- and polyorganic clinical phenotypes of atopic disorders in children |
title_sort | variants of the single nucleotide polymorphisms of thymic stromal lymphopoietin and orsomucoid 1 like protein 3 as predictors of the mono and polyorganic clinical phenotypes of atopic disorders in children |
topic | single-nucleotide polymorphisms mono-organic phenotypes polyorganic phenotypes atopic dermatitis children |
url | https://childshealth.zaslavsky.com.ua/index.php/journal/article/view/1529 |
work_keys_str_mv | AT vdytiatkovskyi variantsofthesinglenucleotidepolymorphismsofthymicstromallymphopoietinandorsomucoid1likeprotein3aspredictorsofthemonoandpolyorganicclinicalphenotypesofatopicdisordersinchildren |