Identification of novel single nucleotide polymorphisms associated with acute respiratory distress syndrome by exome-seq

Katherine Shortt, Suman Chaudhary, Dmitry Grigoryev, Daniel P. Heruth, Lakshmi Venkitachalam, Li Q. Zhang, Shui Q. Ye

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Article numbere111953
JournalPLoS One
Volume9
Issue number11
DOIs
StatePublished - Nov 5 2014
Externally publishedYes

Fingerprint

Exome
Adult Respiratory Distress Syndrome
Polymorphism
single nucleotide polymorphism
Single Nucleotide Polymorphism
Biomarkers
Nucleotides
Genes
Arylsulfatases
Leucine Zippers
Blood Group Antigens
Proline
Leucine
Histones
Introns
biomarkers
Zinc
Transducers
Gases
acute respiratory distress syndrome

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Shortt, K., Chaudhary, S., Grigoryev, D., Heruth, D. P., Venkitachalam, L., Zhang, L. Q., & Ye, S. Q. (2014). Identification of novel single nucleotide polymorphisms associated with acute respiratory distress syndrome by exome-seq. PLoS One, 9(11), [e111953]. https://doi.org/10.1371/journal.pone.0111953

Identification of novel single nucleotide polymorphisms associated with acute respiratory distress syndrome by exome-seq. / Shortt, Katherine; Chaudhary, Suman; Grigoryev, Dmitry; Heruth, Daniel P.; Venkitachalam, Lakshmi; Zhang, Li Q.; Ye, Shui Q.

In: PLoS One, Vol. 9, No. 11, e111953, 05.11.2014.

Research output: Contribution to journalArticle

Shortt, K, Chaudhary, S, Grigoryev, D, Heruth, DP, Venkitachalam, L, Zhang, LQ & Ye, SQ 2014, 'Identification of novel single nucleotide polymorphisms associated with acute respiratory distress syndrome by exome-seq', PLoS One, vol. 9, no. 11, e111953. https://doi.org/10.1371/journal.pone.0111953
Shortt, Katherine ; Chaudhary, Suman ; Grigoryev, Dmitry ; Heruth, Daniel P. ; Venkitachalam, Lakshmi ; Zhang, Li Q. ; Ye, Shui Q. / Identification of novel single nucleotide polymorphisms associated with acute respiratory distress syndrome by exome-seq. In: PLoS One. 2014 ; Vol. 9, No. 11.
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