Exonic variants associated with development of aspirin exacerbated respiratory diseases

Aspirin-exacerbated respiratory disease (AERD) is one phenotype of asthma, often occurring in the form of a severe and sudden attack. Due to the time-consuming nature and difficulty of oral aspirin challenge (OAC) for AERD diagnosis, non-invasive biomarkers have been sought. The aim of this study wa...

Full description

Saved in:
Bibliographic Details
Published in:PloS one 2014-11, Vol.9 (11), p.e111887
Main Authors: Shin, Seung-Woo, Park, Byung Lae, Chang, HunSoo, Park, Jong Sook, Bae, Da-Jeong, Song, Hyun-Ji, Choi, Inseon S, Kim, Mi-Kyeong, Park, Hea-Sim, Kim, Lyoung Hyo, Namgoong, Suhg, Kim, Ji On, Shin, Hyoung Doo, Park, Choon-Sik
Format: Article
Language:English
Subjects:
Adolescent
Adult
Aged
Amino acid sequence
Aspirin
Asthma
Asthma, Aspirin-Induced - diagnosis
Asthma, Aspirin-Induced - genetics
Biology and Life Sciences
Biomarkers
Deoxyribonucleic acid
Diagnostic systems
Disease Progression
DNA
Epidemiology
Exons
Female
Gene expression
Genetic Association Studies
Genetic markers
Genetic Predisposition to Disease
Genetic Variation
Genetics
Genome-Wide Association Study
Genomes
Genotype
Histocompatibility antigen HLA
HLA antigens
Hospitals
Humans
Interdisciplinary aspects
Life sciences
Lung diseases
Male
Mathematical models
Medicine
Medicine and Health Sciences
Middle Aged
Nonsteroidal anti-inflammatory drugs
Polymorphism, Single Nucleotide
Respiratory diseases
Risk Factors
ROC Curve
Single nucleotide polymorphisms
Single-nucleotide polymorphism
Structural damage
Structure-function relationships
Studies
Young Adult
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Aspirin-exacerbated respiratory disease (AERD) is one phenotype of asthma, often occurring in the form of a severe and sudden attack. Due to the time-consuming nature and difficulty of oral aspirin challenge (OAC) for AERD diagnosis, non-invasive biomarkers have been sought. The aim of this study was to identify AERD-associated exonic SNPs and examine the diagnostic potential of a combination of these candidate SNPs to predict AERD. DNA from 165 AERD patients, 397 subjects with aspirin-tolerant asthma (ATA), and 398 normal controls were subjected to an Exome BeadChip assay containing 240K SNPs. 1,023 models (210-1) were generated from combinations of the top 10 SNPs, selected by the p-values in association with AERD. The area under the curve (AUC) of the receiver operating characteristic (ROC) curves was calculated for each model. SNP Function Portal and PolyPhen-2 were used to validate the functional significance of candidate SNPs. An exonic SNP, exm537513 in HLA-DPB1, showed the lowest p-value (p = 3.40×10-8) in its association with AERD risk. From the top 10 SNPs, a combination model of 7 SNPs (exm537513, exm83523, exm1884673, exm538564, exm2264237, exm396794, and exm791954) showed the best AUC of 0.75 (asymptotic p-value of 7.94×10-21), with 34% sensitivity and 93% specificity to discriminate AERD from ATA. Amino acid changes due to exm83523 in CHIA were predicted to be "probably damaging" to the structure and function of the protein, with a high score of '1'. A combination model of seven SNPs may provide a useful, non-invasive genetic marker combination for predicting AERD.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0111887