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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...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4221198/ https://www.ncbi.nlm.nih.gov/pubmed/25372592 http://dx.doi.org/10.1371/journal.pone.0111887 |
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author | 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 |
author_facet | 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 |
author_sort | Shin, Seung-Woo |
collection | PubMed |
description | 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 (2(10)-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. |
format | Online Article Text |
id | pubmed-4221198 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-42211982014-11-12 Exonic Variants Associated with Development of Aspirin Exacerbated Respiratory Diseases 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 PLoS One Research Article 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 (2(10)-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. Public Library of Science 2014-11-05 /pmc/articles/PMC4221198/ /pubmed/25372592 http://dx.doi.org/10.1371/journal.pone.0111887 Text en © 2014 Shin et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article 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 Exonic Variants Associated with Development of Aspirin Exacerbated Respiratory Diseases |
title | Exonic Variants Associated with Development of Aspirin Exacerbated Respiratory Diseases |
title_full | Exonic Variants Associated with Development of Aspirin Exacerbated Respiratory Diseases |
title_fullStr | Exonic Variants Associated with Development of Aspirin Exacerbated Respiratory Diseases |
title_full_unstemmed | Exonic Variants Associated with Development of Aspirin Exacerbated Respiratory Diseases |
title_short | Exonic Variants Associated with Development of Aspirin Exacerbated Respiratory Diseases |
title_sort | exonic variants associated with development of aspirin exacerbated respiratory diseases |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4221198/ https://www.ncbi.nlm.nih.gov/pubmed/25372592 http://dx.doi.org/10.1371/journal.pone.0111887 |
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