Abstract
Acute respiratory distress syndrome (ARDS) is a lung condition characterized by impaired gas exchange with systemic release of inflammatory mediators, causing pulmonary inflammation, vascular leak and hypoxemia. Existing biomarkers have limited effectiveness as diagnostic and therapeutic targets. To identify disease-associating variants in ARDS patients, whole-exome sequencing was performed on 96 ARDS patients, detecting 1,382,399 SNPs. By comparing these exome data to those of the 1000 Genomes Project, we identified a number of single nucleotide polymorphisms (SNP) which are potentially associated with ARDS. 50,190SNPs were found in all case subgroups and controls, of which89 SNPs were associated with susceptibility. We validated three SNPs (rs78142040, rs9605146 and rs3848719) in additional ARDS patients to substantiate their associations with susceptibility, severity and outcome of ARDS. rs78142040 (C>T) occurs within a histone mark (intron 6) of the Arylsulfatase D gene. rs9605146 (G>A) causes a deleterious coding change (proline to leucine) in the XK, Kell blood group complex subunit-related family, member 3 gene. rs3848719 (G>A) is a synonymous SNP in the Zinc-Finger/Leucine-Zipper Co-Transducer NIF1 gene. rs78142040, rs9605146, and rs3848719 are associated significantly with susceptibility to ARDS. rs3848719 is associated with APACHE II score quartile. rs78142040 is associated with 60-day mortality in the overall ARDS patient population. Exome-seq is a powerful tool to identify potential new biomarkers for ARDS. We selectively validated three SNPs which have not been previously associated with ARDS and represent potential new genetic biomarkers for ARDS. Additional validation in larger patient populations and further exploration of underlying molecular mechanisms are warranted.
Highlights
Acute respiratory distress syndrome (ARDS), a severe form of acute lung injury, is characterized by the inflammation and fluid build-up in the alveoli of the lungs, which reduces the ability of oxygen to cross over into the blood stream [1,2]
Identification of novel coding single nucleotide polymorphisms (SNP) associated with the ARDS susceptibility In order to identify novel coding SNPs associated with the ARDS susceptibility, we performed the exome-seq of 96 ARDS patient DNAs
From 169,376 SNPs, there are 49,723 bi-allelic SNPs out of 50,190 total SNPs in all ARDS patient subgroups based on race and initiating etiologies: Caucasian sepsis, Caucasian pneumonia, AfricanAmerican sepsis and African American pneumonia
Summary
Acute respiratory distress syndrome (ARDS), a severe form of acute lung injury, is characterized by the inflammation and fluid build-up in the alveoli of the lungs, which reduces the ability of oxygen to cross over into the blood stream [1,2]. The mortality rate is even higher in cases with common comorbidities such as sepsis with suspected pulmonary source (40.6%) and witnessed aspiration (43.6%) [3]. There is a paucity of effective and specific therapy to ARDS though low tidal volume ventilation has been demonstrated for some therapeutic utilities [5,6,7,8]. This is because the etiology and pathology of the disease are still not well understood and there remains a need for new specific and effective preventative measures and treatments
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
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.
