Exonic Variants Associated with Development of Aspirin Exacerbated Respiratory Diseases

Seung-Woo Shin, Byung Lae Park, HunSoo Chang, Jong Sook Park, Da-Jeong Bae, Hyun-Ji Song, Inseon S Choi, Mi-Kyeong Kim, Hea-Sim Park, Lyoung Hyo Kim, Suhg Namgoong, Ji On Kim, Hyoung Doo Shin and Choon-Sik Park

PLOS ONE, 2014, vol. 9, issue 11, 1-8

Abstract: 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.

Date: 2014
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Persistent link: https://EconPapers.repec.org/RePEc:plo:pone00:0111887

DOI: 10.1371/journal.pone.0111887

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