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Component 1 Inhibitor Missense (Val480Met) Variant Is Associated With Gene Expression and Sepsis Development in Neonatal Lung Disease
BACKGROUND: Neonatal lung disease has a multifaceted etiopathology, including an explosive inflammatory sequence in the immature lung. Complement component 1 Esterase INHibitor (C1INH) is implicated in controlling inflammation in response to infection/injury. AIM: To explore for the first time the a...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9163386/ https://www.ncbi.nlm.nih.gov/pubmed/35669402 http://dx.doi.org/10.3389/fped.2022.779511 |
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author | Elngar, Enas F. Azzam, Mona A. Gobarah, Ayman A. Toraih, Eman A. Fawzy, Manal S. AbdAllah, Nouran B. |
author_facet | Elngar, Enas F. Azzam, Mona A. Gobarah, Ayman A. Toraih, Eman A. Fawzy, Manal S. AbdAllah, Nouran B. |
author_sort | Elngar, Enas F. |
collection | PubMed |
description | BACKGROUND: Neonatal lung disease has a multifaceted etiopathology, including an explosive inflammatory sequence in the immature lung. Complement component 1 Esterase INHibitor (C1INH) is implicated in controlling inflammation in response to infection/injury. AIM: To explore for the first time the association of the C1INH rs4926 (Val480Met) variant and circulatory transcript expression levels in the neonates that had evidence of lung disease and the clinic-laboratory data. METHODS: A total of 139 unrelated neonates were enrolled in this case-control study. C1INH genotyping and expression analyses were done using TaqMan Genotyping and Real-Time qPCR, respectively. RESULTS: A/A genotype carriers were two times more likely to develop in newborns with lung disease under homozygote (A/A vs. G/G: OR = 2.66, 95%CI = 1.03-6.87, p = 0.039) and recessive (A/A vs. G/G-A/G: OR = 2.42, 95%CI = 1.07-6.06, p = 0.047) models. Also, a higher frequency of A/A genotype was observed in the patient's cohort complicated with sepsis (44.2 vs. 14.3%, p = 0.002). Neonates with lung disease with A variant had more risk for developing sepsis under homozygote (A/A vs. G/G: OR = 5.19, 95%CI = 1.73-15.6, p = 0.002), dominant (A/G-A/A vs. G/G: OR = 2.39, 95%CI = 1.02-5.58, p = 0.041), and recessive (A/A vs. G/G-A/G: OR = 5.38, 95%CI = 1.86-15.5, p < 0.001) models. Regression analysis revealed rs4926(*)A/A genotype as an independent predictor risk factor for sepsis development in cohorts with lung disease (adjusted OR = 4.26, 95%CI = 1.38-13.1, p = 0.012). The circulatory transcript was significantly downregulated in neonates with lung disease in whom rs4926(*)A/A carriers had the least expression levels (median: −2.86, IQR: −3.55 to −1.71; p < 0.001). ROC curve analysis revealed C1INH expression could differentiate between cohorts with/without subsequent development of sepsis, and the discrimination ability was enhanced when combined with circulatory IL-6 and CRP levels (AUC = 0.926, 95%CI = 0.87-0.97). CONCLUSION: The C1INH rs4926 variant might play an essential role in the susceptibility to neonatal lung disease and could predict sepsis development in this cohort. Furthermore, the circulatory expression levels of this gene were downregulated in the neonatal lung disease cohort, supporting its potential role in the pathophysiology of this disorder, and highlighting its promising role in future targeted therapy. |
format | Online Article Text |
id | pubmed-9163386 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-91633862022-06-05 Component 1 Inhibitor Missense (Val480Met) Variant Is Associated With Gene Expression and Sepsis Development in Neonatal Lung Disease Elngar, Enas F. Azzam, Mona A. Gobarah, Ayman A. Toraih, Eman A. Fawzy, Manal S. AbdAllah, Nouran B. Front Pediatr Pediatrics BACKGROUND: Neonatal lung disease has a multifaceted etiopathology, including an explosive inflammatory sequence in the immature lung. Complement component 1 Esterase INHibitor (C1INH) is implicated in controlling inflammation in response to infection/injury. AIM: To explore for the first time the association of the C1INH rs4926 (Val480Met) variant and circulatory transcript expression levels in the neonates that had evidence of lung disease and the clinic-laboratory data. METHODS: A total of 139 unrelated neonates were enrolled in this case-control study. C1INH genotyping and expression analyses were done using TaqMan Genotyping and Real-Time qPCR, respectively. RESULTS: A/A genotype carriers were two times more likely to develop in newborns with lung disease under homozygote (A/A vs. G/G: OR = 2.66, 95%CI = 1.03-6.87, p = 0.039) and recessive (A/A vs. G/G-A/G: OR = 2.42, 95%CI = 1.07-6.06, p = 0.047) models. Also, a higher frequency of A/A genotype was observed in the patient's cohort complicated with sepsis (44.2 vs. 14.3%, p = 0.002). Neonates with lung disease with A variant had more risk for developing sepsis under homozygote (A/A vs. G/G: OR = 5.19, 95%CI = 1.73-15.6, p = 0.002), dominant (A/G-A/A vs. G/G: OR = 2.39, 95%CI = 1.02-5.58, p = 0.041), and recessive (A/A vs. G/G-A/G: OR = 5.38, 95%CI = 1.86-15.5, p < 0.001) models. Regression analysis revealed rs4926(*)A/A genotype as an independent predictor risk factor for sepsis development in cohorts with lung disease (adjusted OR = 4.26, 95%CI = 1.38-13.1, p = 0.012). The circulatory transcript was significantly downregulated in neonates with lung disease in whom rs4926(*)A/A carriers had the least expression levels (median: −2.86, IQR: −3.55 to −1.71; p < 0.001). ROC curve analysis revealed C1INH expression could differentiate between cohorts with/without subsequent development of sepsis, and the discrimination ability was enhanced when combined with circulatory IL-6 and CRP levels (AUC = 0.926, 95%CI = 0.87-0.97). CONCLUSION: The C1INH rs4926 variant might play an essential role in the susceptibility to neonatal lung disease and could predict sepsis development in this cohort. Furthermore, the circulatory expression levels of this gene were downregulated in the neonatal lung disease cohort, supporting its potential role in the pathophysiology of this disorder, and highlighting its promising role in future targeted therapy. Frontiers Media S.A. 2022-05-20 /pmc/articles/PMC9163386/ /pubmed/35669402 http://dx.doi.org/10.3389/fped.2022.779511 Text en Copyright © 2022 Elngar, Azzam, Gobarah, Toraih, Fawzy and AbdAllah. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Pediatrics Elngar, Enas F. Azzam, Mona A. Gobarah, Ayman A. Toraih, Eman A. Fawzy, Manal S. AbdAllah, Nouran B. Component 1 Inhibitor Missense (Val480Met) Variant Is Associated With Gene Expression and Sepsis Development in Neonatal Lung Disease |
title | Component 1 Inhibitor Missense (Val480Met) Variant Is Associated With Gene Expression and Sepsis Development in Neonatal Lung Disease |
title_full | Component 1 Inhibitor Missense (Val480Met) Variant Is Associated With Gene Expression and Sepsis Development in Neonatal Lung Disease |
title_fullStr | Component 1 Inhibitor Missense (Val480Met) Variant Is Associated With Gene Expression and Sepsis Development in Neonatal Lung Disease |
title_full_unstemmed | Component 1 Inhibitor Missense (Val480Met) Variant Is Associated With Gene Expression and Sepsis Development in Neonatal Lung Disease |
title_short | Component 1 Inhibitor Missense (Val480Met) Variant Is Associated With Gene Expression and Sepsis Development in Neonatal Lung Disease |
title_sort | component 1 inhibitor missense (val480met) variant is associated with gene expression and sepsis development in neonatal lung disease |
topic | Pediatrics |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9163386/ https://www.ncbi.nlm.nih.gov/pubmed/35669402 http://dx.doi.org/10.3389/fped.2022.779511 |
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