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Genetic polymorphism of ADAM17 and decreased bilirubin levels are associated with allergic march in the Korean population

BACKGROUND: The “allergic march” refers to changes in the frequency and intensity of allergic diseases with age. Classically, the allergic march begins with atopic dermatitis in infancy and leads to asthma and rhinitis as it continues. There are many factors that induce the allergic march; however,...

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Autores principales: Jung, Jaemee, Hwang, Dahyun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8822644/
https://www.ncbi.nlm.nih.gov/pubmed/35130903
http://dx.doi.org/10.1186/s12920-022-01170-7
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author Jung, Jaemee
Hwang, Dahyun
author_facet Jung, Jaemee
Hwang, Dahyun
author_sort Jung, Jaemee
collection PubMed
description BACKGROUND: The “allergic march” refers to changes in the frequency and intensity of allergic diseases with age. Classically, the allergic march begins with atopic dermatitis in infancy and leads to asthma and rhinitis as it continues. There are many factors that induce the allergic march; however, TNF-α may play an important role in inducing inflammation. Therefore, the therapeutic potential of TNF alpha-targeting agents is being considered for allergic march treatment. METHODS: We performed a correlation study to determine whether genetic polymorphisms of ADAM17 and clinical serum values between allergic and normal groups affect disease development by using the cohort data of the Korean genome epidemiologic research project. Gene association study was performed using PLINK version 1.07 (http://pngu.mgh.harvard.edu/–purcell/plink) and other statistical analysis was performed using PASW Statistics (version 18.0, SPSS Inc. Chicago, IL, USA). RESULTS: ADAM17 (also called TNF-α converting enzyme or TACE) showed a statistically significant association with the allergic march. The 13 and 8 SNPs in ADAM17 were significantly associated with asthma and allergies, respectively. Among them, on average, SNP of rs6432011 showed the greatest statistical correlation with asthma (P = 0.00041, OR = 1.95, 95% CI 1.35–2.82) and allergies (P = 0.02918, OR = 1.35, 95% CI 1.03–1.78). The effect of SNPs in ADAM17 on transcription factor binding was confirmed using RegulomeDB. The six SNPs are located in the genomic expression quantitative trait loci (eQTL) region and can affect transcription factor binding and gene expression. In clinical serum analysis, bilirubin levels were significantly decreased in the allergic group. The multivariate logistic regression analysis revealed that the low-bilirubin groups indicated a 3.22-fold increase in the prevalence of asthma compared with the high-bilirubin group. CONCLUSIONS: The ADAM17 gene and low bilirubin levels are associated with the allergic march in the Korean population, which can provide new guidelines for managing this disease progression phenomena. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12920-022-01170-7.
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spelling pubmed-88226442022-02-08 Genetic polymorphism of ADAM17 and decreased bilirubin levels are associated with allergic march in the Korean population Jung, Jaemee Hwang, Dahyun BMC Med Genomics Research BACKGROUND: The “allergic march” refers to changes in the frequency and intensity of allergic diseases with age. Classically, the allergic march begins with atopic dermatitis in infancy and leads to asthma and rhinitis as it continues. There are many factors that induce the allergic march; however, TNF-α may play an important role in inducing inflammation. Therefore, the therapeutic potential of TNF alpha-targeting agents is being considered for allergic march treatment. METHODS: We performed a correlation study to determine whether genetic polymorphisms of ADAM17 and clinical serum values between allergic and normal groups affect disease development by using the cohort data of the Korean genome epidemiologic research project. Gene association study was performed using PLINK version 1.07 (http://pngu.mgh.harvard.edu/–purcell/plink) and other statistical analysis was performed using PASW Statistics (version 18.0, SPSS Inc. Chicago, IL, USA). RESULTS: ADAM17 (also called TNF-α converting enzyme or TACE) showed a statistically significant association with the allergic march. The 13 and 8 SNPs in ADAM17 were significantly associated with asthma and allergies, respectively. Among them, on average, SNP of rs6432011 showed the greatest statistical correlation with asthma (P = 0.00041, OR = 1.95, 95% CI 1.35–2.82) and allergies (P = 0.02918, OR = 1.35, 95% CI 1.03–1.78). The effect of SNPs in ADAM17 on transcription factor binding was confirmed using RegulomeDB. The six SNPs are located in the genomic expression quantitative trait loci (eQTL) region and can affect transcription factor binding and gene expression. In clinical serum analysis, bilirubin levels were significantly decreased in the allergic group. The multivariate logistic regression analysis revealed that the low-bilirubin groups indicated a 3.22-fold increase in the prevalence of asthma compared with the high-bilirubin group. CONCLUSIONS: The ADAM17 gene and low bilirubin levels are associated with the allergic march in the Korean population, which can provide new guidelines for managing this disease progression phenomena. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12920-022-01170-7. BioMed Central 2022-02-07 /pmc/articles/PMC8822644/ /pubmed/35130903 http://dx.doi.org/10.1186/s12920-022-01170-7 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Jung, Jaemee
Hwang, Dahyun
Genetic polymorphism of ADAM17 and decreased bilirubin levels are associated with allergic march in the Korean population
title Genetic polymorphism of ADAM17 and decreased bilirubin levels are associated with allergic march in the Korean population
title_full Genetic polymorphism of ADAM17 and decreased bilirubin levels are associated with allergic march in the Korean population
title_fullStr Genetic polymorphism of ADAM17 and decreased bilirubin levels are associated with allergic march in the Korean population
title_full_unstemmed Genetic polymorphism of ADAM17 and decreased bilirubin levels are associated with allergic march in the Korean population
title_short Genetic polymorphism of ADAM17 and decreased bilirubin levels are associated with allergic march in the Korean population
title_sort genetic polymorphism of adam17 and decreased bilirubin levels are associated with allergic march in the korean population
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8822644/
https://www.ncbi.nlm.nih.gov/pubmed/35130903
http://dx.doi.org/10.1186/s12920-022-01170-7
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