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Association of SNP–SNP Interactions of Surfactant Protein Genes with Pediatric Acute Respiratory Failure

The hallmarks of pediatric acute respiratory failure (ARF) are dysregulated inflammation and surfactant dysfunction. The objective is to study association of surfactant protein (SP) genes’ single nucleotide polymorphisms (SNPs) with ARF and its morbidity: pulmonary dysfunction at discharge (PDAD), e...

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Autores principales: Gandhi, Chintan K., Chen, Chixiang, Wu, Rongling, Yang, Lili, Thorenoor, Nithyananda, Thomas, Neal J., DiAngelo, Susan L., Spear, Debbie, Keim, Garrett, Yehya, Nadir, Floros, Joanna
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7231046/
https://www.ncbi.nlm.nih.gov/pubmed/32326132
http://dx.doi.org/10.3390/jcm9041183
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author Gandhi, Chintan K.
Chen, Chixiang
Wu, Rongling
Yang, Lili
Thorenoor, Nithyananda
Thomas, Neal J.
DiAngelo, Susan L.
Spear, Debbie
Keim, Garrett
Yehya, Nadir
Floros, Joanna
author_facet Gandhi, Chintan K.
Chen, Chixiang
Wu, Rongling
Yang, Lili
Thorenoor, Nithyananda
Thomas, Neal J.
DiAngelo, Susan L.
Spear, Debbie
Keim, Garrett
Yehya, Nadir
Floros, Joanna
author_sort Gandhi, Chintan K.
collection PubMed
description The hallmarks of pediatric acute respiratory failure (ARF) are dysregulated inflammation and surfactant dysfunction. The objective is to study association of surfactant protein (SP) genes’ single nucleotide polymorphisms (SNPs) with ARF and its morbidity: pulmonary dysfunction at discharge (PDAD), employing a single-, two-, and three-SNP interaction model. We enrolled 468 newborn controls and 248 children aged ≤ 24 months with ARF; 86 developed PDAD. Using quantitative genetic principles, we tested the association of SP genes SNPs with ARF and PDAD. We observed a dominant effect of rs4715 of the SFTPC on ARF risk. In a three-SNP model, we found (a) 34 significant interactions among SNPs of SFTPA1, SFTPA2, and SFTPC associated with ARF (p = 0.000000002–0.05); 15 and 19 of those interactions were associated with increased and decreased risk for ARF, respectively; (b) intergenic SNP–SNP interactions of both hydrophobic and hydrophilic SP genes associated with PDAD (p = 0.00002–0.03). The majority of intra- and intergenic interactions associated with ARF involve the SFTPA2 SNPs, whereas most of the intra- and intergenic interactions associated with PDAD are of SFTPA1 SNPs. We also observed a dominant effect of haplotypes GG of SFTPA1 associated with increased and AA of SFTPC associated with decreased ARF risk (p = 0.02). To the best of our knowledge, this is the first study showing an association of complex interactions of SP genes with ARF and PDAD. Our data indicate that SP genes polymorphisms may contribute to ARF pathogenesis and subsequent PDAD and/or may serve as markers for disease susceptibility in healthy children.
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spelling pubmed-72310462020-05-22 Association of SNP–SNP Interactions of Surfactant Protein Genes with Pediatric Acute Respiratory Failure Gandhi, Chintan K. Chen, Chixiang Wu, Rongling Yang, Lili Thorenoor, Nithyananda Thomas, Neal J. DiAngelo, Susan L. Spear, Debbie Keim, Garrett Yehya, Nadir Floros, Joanna J Clin Med Article The hallmarks of pediatric acute respiratory failure (ARF) are dysregulated inflammation and surfactant dysfunction. The objective is to study association of surfactant protein (SP) genes’ single nucleotide polymorphisms (SNPs) with ARF and its morbidity: pulmonary dysfunction at discharge (PDAD), employing a single-, two-, and three-SNP interaction model. We enrolled 468 newborn controls and 248 children aged ≤ 24 months with ARF; 86 developed PDAD. Using quantitative genetic principles, we tested the association of SP genes SNPs with ARF and PDAD. We observed a dominant effect of rs4715 of the SFTPC on ARF risk. In a three-SNP model, we found (a) 34 significant interactions among SNPs of SFTPA1, SFTPA2, and SFTPC associated with ARF (p = 0.000000002–0.05); 15 and 19 of those interactions were associated with increased and decreased risk for ARF, respectively; (b) intergenic SNP–SNP interactions of both hydrophobic and hydrophilic SP genes associated with PDAD (p = 0.00002–0.03). The majority of intra- and intergenic interactions associated with ARF involve the SFTPA2 SNPs, whereas most of the intra- and intergenic interactions associated with PDAD are of SFTPA1 SNPs. We also observed a dominant effect of haplotypes GG of SFTPA1 associated with increased and AA of SFTPC associated with decreased ARF risk (p = 0.02). To the best of our knowledge, this is the first study showing an association of complex interactions of SP genes with ARF and PDAD. Our data indicate that SP genes polymorphisms may contribute to ARF pathogenesis and subsequent PDAD and/or may serve as markers for disease susceptibility in healthy children. MDPI 2020-04-20 /pmc/articles/PMC7231046/ /pubmed/32326132 http://dx.doi.org/10.3390/jcm9041183 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Gandhi, Chintan K.
Chen, Chixiang
Wu, Rongling
Yang, Lili
Thorenoor, Nithyananda
Thomas, Neal J.
DiAngelo, Susan L.
Spear, Debbie
Keim, Garrett
Yehya, Nadir
Floros, Joanna
Association of SNP–SNP Interactions of Surfactant Protein Genes with Pediatric Acute Respiratory Failure
title Association of SNP–SNP Interactions of Surfactant Protein Genes with Pediatric Acute Respiratory Failure
title_full Association of SNP–SNP Interactions of Surfactant Protein Genes with Pediatric Acute Respiratory Failure
title_fullStr Association of SNP–SNP Interactions of Surfactant Protein Genes with Pediatric Acute Respiratory Failure
title_full_unstemmed Association of SNP–SNP Interactions of Surfactant Protein Genes with Pediatric Acute Respiratory Failure
title_short Association of SNP–SNP Interactions of Surfactant Protein Genes with Pediatric Acute Respiratory Failure
title_sort association of snp–snp interactions of surfactant protein genes with pediatric acute respiratory failure
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7231046/
https://www.ncbi.nlm.nih.gov/pubmed/32326132
http://dx.doi.org/10.3390/jcm9041183
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