Abstract
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.
Highlights
Acute respiratory failure (ARF), defined as the failure of the respiratory system to provide oxygen and/or eliminate carbon dioxide, is a common cause of critical illness in children [1]
Our findings demonstrate association of single single nucleotide polymorphisms (SNPs), SNP–SNP interactions and haplotypes of surfactant protein (SP) genes with ARF
The majority of SNP interactions associated with increased ARF risk involve SFTPA2 SNPs, while the majority of SNP interactions associated with pulmonary dysfunction at discharge (PDAD) risk involve SFTPA1
Summary
Acute respiratory failure (ARF), defined as the failure of the respiratory system to provide oxygen and/or eliminate carbon dioxide, is a common cause of critical illness in children [1]. ARF can be defined based on blood gas abnormalities: partial pressure of carbon dioxide > 55 mm Hg, partial pressure of oxygen < 60 mm Hg, and/or pH < 7.35 [2]. The incidence of ARF is inversely related to age and it is one of the common cause of death in children ≤ 24 months [4]. Respiratory infections and direct lung injury are the most common causes of ARF in children [4]. It is conceivable that an underlying genetic predisposition, along with environmental factors, may contribute to the cause and pathogenesis of complex diseases such as pediatric ARF and its progression. The role of genetics in pediatric ARF is under studied
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
