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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MDPI AG
2020-04-01
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| Series: | Journal of Clinical Medicine |
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| Online Access: | https://www.mdpi.com/2077-0383/9/4/1183 |
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| author | Chintan K. Gandhi Chixiang Chen Rongling Wu Lili Yang Nithyananda Thorenoor Neal J. Thomas Susan L. DiAngelo Debbie Spear Garrett Keim Nadir Yehya Joanna Floros |
| author_facet | Chintan K. Gandhi Chixiang Chen Rongling Wu Lili Yang Nithyananda Thorenoor Neal J. Thomas Susan L. DiAngelo Debbie Spear Garrett Keim Nadir Yehya Joanna Floros |
| author_sort | Chintan K. Gandhi |
| collection | DOAJ |
| 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 <i>SFTPC</i> on ARF risk. In a three-SNP model, we found (a) 34 significant interactions among SNPs of <i>SFTPA1, SFTPA2,</i> and <i>SFTPC</i> associated with ARF (<i>p</i> = 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 (<i>p</i> = 0.00002–0.03). The majority of intra- and intergenic interactions associated with ARF involve the <i>SFTPA2</i> SNPs, whereas most of the intra- and intergenic interactions associated with PDAD are of <i>SFTPA1</i> SNPs. We also observed a dominant effect of haplotypes GG of <i>SFTPA1</i> associated with increased and AA of <i>SFTPC</i> associated with decreased ARF risk (<i>p</i> = 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. |
| first_indexed | 2024-03-10T20:20:00Z |
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| institution | Directory Open Access Journal |
| issn | 2077-0383 |
| language | English |
| last_indexed | 2024-03-10T20:20:00Z |
| publishDate | 2020-04-01 |
| publisher | MDPI AG |
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| series | Journal of Clinical Medicine |
| spelling | doaj.art-1947ccecda0e4b9a93d163036eab80d82023-11-19T22:13:46ZengMDPI AGJournal of Clinical Medicine2077-03832020-04-0194118310.3390/jcm9041183Association of SNP–SNP Interactions of Surfactant Protein Genes with Pediatric Acute Respiratory FailureChintan K. Gandhi0Chixiang Chen1Rongling Wu2Lili Yang3Nithyananda Thorenoor4Neal J. Thomas5Susan L. DiAngelo6Debbie Spear7Garrett Keim8Nadir Yehya9Joanna Floros10Center for Host defense, Inflammation, and Lung Disease (CHILD) Research, Department of Pediatrics, Pennsylvania State University College of Medicine, Hershey, PA 17033, USADepartment of Public Health Science, Pennsylvania State University College of Medicine, Hershey, PA 17033, USADepartment of Public Health Science, Pennsylvania State University College of Medicine, Hershey, PA 17033, USASchool of First Clinical Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, ChinaCenter for Host defense, Inflammation, and Lung Disease (CHILD) Research, Department of Pediatrics, Pennsylvania State University College of Medicine, Hershey, PA 17033, USACenter for Host defense, Inflammation, and Lung Disease (CHILD) Research, Department of Pediatrics, Pennsylvania State University College of Medicine, Hershey, PA 17033, USACenter for Host defense, Inflammation, and Lung Disease (CHILD) Research, Department of Pediatrics, Pennsylvania State University College of Medicine, Hershey, PA 17033, USACenter for Host defense, Inflammation, and Lung Disease (CHILD) Research, Department of Pediatrics, Pennsylvania State University College of Medicine, Hershey, PA 17033, USADepartment of Pediatrics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USADepartment of Pediatrics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USACenter for Host defense, Inflammation, and Lung Disease (CHILD) Research, Department of Pediatrics, Pennsylvania State University College of Medicine, Hershey, PA 17033, USAThe 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 <i>SFTPC</i> on ARF risk. In a three-SNP model, we found (a) 34 significant interactions among SNPs of <i>SFTPA1, SFTPA2,</i> and <i>SFTPC</i> associated with ARF (<i>p</i> = 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 (<i>p</i> = 0.00002–0.03). The majority of intra- and intergenic interactions associated with ARF involve the <i>SFTPA2</i> SNPs, whereas most of the intra- and intergenic interactions associated with PDAD are of <i>SFTPA1</i> SNPs. We also observed a dominant effect of haplotypes GG of <i>SFTPA1</i> associated with increased and AA of <i>SFTPC</i> associated with decreased ARF risk (<i>p</i> = 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.https://www.mdpi.com/2077-0383/9/4/1183SNP–SNP interactionPediatric acute respiratory failureSurfactant protein gene A1 (<i>SFTPA1</i>), <i>SFTPA2</i><i>SFTPB</i><i>SFTPC</i><i>SFTPD</i> |
| spellingShingle | Chintan K. Gandhi Chixiang Chen Rongling Wu Lili Yang Nithyananda Thorenoor Neal J. Thomas Susan L. DiAngelo Debbie Spear Garrett Keim Nadir Yehya Joanna Floros Association of SNP–SNP Interactions of Surfactant Protein Genes with Pediatric Acute Respiratory Failure Journal of Clinical Medicine SNP–SNP interaction Pediatric acute respiratory failure Surfactant protein gene A1 (<i>SFTPA1</i>), <i>SFTPA2</i> <i>SFTPB</i> <i>SFTPC</i> <i>SFTPD</i> |
| 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 | SNP–SNP interaction Pediatric acute respiratory failure Surfactant protein gene A1 (<i>SFTPA1</i>), <i>SFTPA2</i> <i>SFTPB</i> <i>SFTPC</i> <i>SFTPD</i> |
| url | https://www.mdpi.com/2077-0383/9/4/1183 |
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