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

Autor: Suman Chaudhary, Li Q. Zhang, Dmitry N. Grigoryev, Lakshmi Venkitachalam, Katherine Shortt, Daniel P. Heruth, Shui Qing Ye
Jazyk: angličtina
Rok vydání: 2014
Předmět:
Male
ARDS
Adolescent
lcsh:Medicine
Single-nucleotide polymorphism
Comorbidity
Biology
Bioinformatics
Polymorphism
Single Nucleotide
Sepsis
Young Adult
03 medical and health sciences
0302 clinical medicine
Polymorphism (computer science)
Genetics
Medicine and Health Sciences
medicine
Humans
SNP
Exome
Genetic Predisposition to Disease
Allele
Child
lcsh:Science
Alleles
Genetic Association Studies
030304 developmental biology
Clinical Genetics
Evolutionary Biology
Respiratory Distress Syndrome
0303 health sciences
Multidisciplinary
lcsh:R
Personalized Medicine
Case-control study
Biology and Life Sciences
High-Throughput Nucleotide Sequencing
Genomics
medicine.disease
3. Good health
Case-Control Studies
Child
Preschool
030220 oncology & carcinogenesis
Female
lcsh:Q
Population Genetics
Research Article
Signal Transduction
Zdroj: PLoS ONE, Vol 9, Iss 11, p e111953 (2014)
PLoS ONE
ISSN: 1932-6203
7814-2040
Popis: 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.
Databáze: OpenAIRE
Externí odkaz: