Genetics of Acute Respiratory Distress Syndrome: Challenges, Approaches, Surfactant Proteins as Candidate Genes

Floros, Joanna; Pavlović, Jelena

doi:10.1055/s-2003-39015

Cited by 12 publications

(6 citation statements)

References 71 publications

(110 reference statements)

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“…Additional identi cation of the 3 surfactant genes in GP7 and in the unrelated ARDS cohort was not evident in the family cohort as there was only 1 family member that had 2 out of the 3 gene variants. Surfactant genes have been implicated in ARDS across multiple studies and our nding is in line with their documented role [39][40][41][42].…”

Section: Discussionsupporting

confidence: 84%

“…Family members and control cohort were recruited, enrolled after informed consent under a protocol approved by the Human Subjects Protection O ce and Institutional Review Board from the Pennsylvania State University College of Medicine. Three sets of samples were collected: primary ARDS case, and related family members; a third set of samples from unrelated ARDS subjects used in the present study were collected as previously described [40,41]. Together, we analyzed a total of 18 samples.…”

Section: Study Information and Sample Collectionmentioning

confidence: 99%

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Characterizing a Focused Landscape of Familial Acute Respiratory Distress Syndrome

2020

Biomark Applic

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Background Acute respiratory distress syndrome (ARDS) affects approximately 190,600 patients per year in the United States, with mortality up to 45%. ARDS can occur as primary disease due to various factors (e.g. bacterial or viral pneumonia, gastric aspiration, lung contusion, toxic inhalation, and near drowning) or as secondary disease due to sepsis, pancreatitis, severe trauma, massive blood transfusion, and burn.We hypothesized that ARDS-affected individuals have patterns of variants in their physiological repertoire that can be tracked and utilized to complement clinical diagnosis and/or clinical monitoring. MethodsThe goals of this study were to: (1) characterize the landscape of variants within protein coding but we also studied UTR regions in ARDS using an Exome sequencing approach; (2), determine the variations in signaling pathways across ARDS; and (3) use computational approaches to explore the functional consequences of ARDS. Towards this we assessed an ARDS-affected individual in the context of unaffected individuals from the same family as well as unrelated ARDS cases, in order to elucidate underlying inheritance patterns of "private variants". Private variants consist of variants shared by ARDS cases but not found in unaffected individuals. Results Whole exome sequencing yielded 3,516 variants represented by 2,354 genes. Of these, 128 variants were shared across all ARDS cases. Of these, there were 24 unique variants represented by 9 ARDS genes shared by the primary ARDS-case and unrelated individuals with ARDS. The overall genes identi ed and subsequent analysis, demonstrate that there are important biological pathways that distinguish ARDS cases from or from non-ARDS. These pathways include: cell-to-cell signaling interaction, cell growth and proliferation and cell morphology. The data also show a coordinated effort amongst biological processes such as liver hyperproliferation and cell death that underlie the pathogenesis of ARDS. Conclusions These in-silico discoveries demonstrate a role for private variants shared by ARDS cases to be leveraged as biomarkers for clinical diagnosis and/or monitoring of ARDS.

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Section: Discussionsupporting

confidence: 84%

Section: Study Information and Sample Collectionmentioning

confidence: 99%

Characterizing a Focused Landscape of Familial Acute Respiratory Distress Syndrome

2020

Biomark Applic

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“…5 ALI /ARDS, however, data indicate that genetic predisposition plays a role [7,8,9]. In the development of the syndrome, various inflammatory cells such as polymorphonuclear neutrophils, alveolar macrophages and platelets participate [for review see ref .…”

Section: Accepted M Manuscriptmentioning

confidence: 99%

Phospholipase A2 subclasses in acute respiratory distress syndrome

Kitsiouli

Nakos

Lekka

2009

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Diseas

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Phospholipases A2 (PLA2) catalyse the cleavage of fatty acids esterified at the sn-2 position of glycerophospholipids. In acute lung injury-acute respiratory distress syndrome (ALI-ARDS) several distinct isoenzymes appear in lung cells and fluid. Some are capable to trigger molecular events leading to enhanced inflammation and lung damage and others have a role in lung surfactant recycling preserving lung function: Secreted forms (groups sPLA2-IIA, -V, -X) can directly hydrolyze surfactant phospholipids. Cytosolic PLA2 (cPLA2-IVA) requiring Ca2+ has a preference for arachidonate, the precursor of eicosanoids which participate in the inflammatory response in the lung. Ca(2+)-independent intracellular PLA2s (iPLA2) take part in surfactant phospholipids turnover within alveolar cells. Acidic Ca(2+)-independent PLA2 (aiPLA2), of lysosomal origin, has additionally antioxidant properties, (peroxiredoxin VI activity), and participates in the formation of dipalmitoyl-phosphatidylcholine in lung surfactant. PAF-AH degrades PAF, a potent mediator of inflammation, and oxidatively fragmented phospholipids but also leads to toxic metabolites. Therefore, the regulation of PLA2 isoforms could be a valuable approach for ARDS treatment.

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“…Family members and control cohort were recruited, enrolled after informed consent under a protocol approved by the Human Subjects Protection Office and Institutional Review Board from the Pennsylvania State University College of Medicine. Three sets of samples were collected: primary ARDS case, and related family members; a third set of samples from unrelated ARDS subjects used in the present study were collected as previously described [40,41]. Together, we analyzed a total of 18 samples.…”

Section: Study Information and Sample Collectionmentioning

confidence: 99%

Characterizing a focused landscape of familial acute respiratory distress syndrome

Toby¹,

Thomas²,

Thorenoor³

et al. 2019

Preprint

Self Cite

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Background Acute respiratory distress syndrome (ARDS) affects approximately 190,600 patients per year in the United States, with mortality up to 45%. ARDS can occur as primary disease due to various factors (e.g. bacterial or viral pneumonia, gastric aspiration, lung contusion, toxic inhalation, and near drowning) or as secondary disease due to sepsis, pancreatitis, severe trauma, massive blood transfusion, and burn. We hypothesized that ARDS-affected individuals have patterns of variants in their physiological repertoire that can be tracked and utilized to complement clinical diagnosis and/or clinical monitoring. Methods The goals of this study were to: (1) characterize the landscape of variants within protein coding but we also studied UTR regions in ARDS using an Exome sequencing approach; (2), determine the variations in signaling pathways across ARDS; and (3) use computational approaches to explore the functional consequences of ARDS. Towards this we assessed an ARDS-affected individual in the context of unaffected individuals from the same family as well as unrelated ARDS cases, in order to elucidate underlying inheritance patterns of “private variants”. Private variants consist of variants shared by ARDS cases but not found in unaffected individuals. Results Whole exome sequencing yielded 3,516 variants represented by 2,354 genes. Of these, 128 variants were shared across all ARDS cases. Of these, there were 24 unique variants represented by 9 ARDS genes shared by the primary ARDS-case and unrelated individuals with ARDS. The overall genes identified and subsequent analysis, demonstrate that there are important biological pathways that distinguish ARDS cases from or from non-ARDS. These pathways include: cell-to-cell signaling interaction, cell growth and proliferation and cell morphology. The data also show a coordinated effort amongst biological processes such as liver hyperproliferation and cell death that underlie the pathogenesis of ARDS. Conclusions These in-silico discoveries demonstrate a role for private variants shared by ARDS cases to be leveraged as biomarkers for clinical diagnosis and/or monitoring of ARDS.

show abstract

Genetics of Acute Respiratory Distress Syndrome: Challenges, Approaches, Surfactant Proteins as Candidate Genes

Cited by 12 publications

References 71 publications

Characterizing a Focused Landscape of Familial Acute Respiratory Distress Syndrome

Characterizing a Focused Landscape of Familial Acute Respiratory Distress Syndrome

Phospholipase A2 subclasses in acute respiratory distress syndrome

Characterizing a focused landscape of familial acute respiratory distress syndrome

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