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Exonic variants associated with development of aspirin exacerbated respiratory diseases.

Shin SW, Park BL, Chang H, Park JS, Bae DJ, Song HJ, Choi IS, Kim MK, Park HS, Kim LH, Namgoong S, Kim JO, Shin HD, Park CS - PLoS ONE (2014)

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Genome Research Center for Allergy and Respiratory Diseases, Division of Allergy and Respiratory Medicine, Soonchunhyang University Bucheon Hospital, Bucheon, Republic of Korea.

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.

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Manhattan plot of the p-values of 54,555 autosomal SNPs in association with AERD.
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pone-0111887-g002: Manhattan plot of the p-values of 54,555 autosomal SNPs in association with AERD.

Mentions: The p-values of all SNPs in association with the risk of AERD under the additive mode are presented in a Manhattan plot (Fig. 2). The exm537513 on HLA-DPB1 showed the lowest p-value of 3.4×10−8 (OR: 3.28,) in association with AERD. The p-value remained significant after multiple comparisons using Bonferroni’s correction (p = 0.0082).


Exonic variants associated with development of aspirin exacerbated respiratory diseases.

Shin SW, Park BL, Chang H, Park JS, Bae DJ, Song HJ, Choi IS, Kim MK, Park HS, Kim LH, Namgoong S, Kim JO, Shin HD, Park CS - PLoS ONE (2014)

Manhattan plot of the p-values of 54,555 autosomal SNPs in association with AERD.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4221198&req=5

pone-0111887-g002: Manhattan plot of the p-values of 54,555 autosomal SNPs in association with AERD.
Mentions: The p-values of all SNPs in association with the risk of AERD under the additive mode are presented in a Manhattan plot (Fig. 2). The exm537513 on HLA-DPB1 showed the lowest p-value of 3.4×10−8 (OR: 3.28,) in association with AERD. The p-value remained significant after multiple comparisons using Bonferroni’s correction (p = 0.0082).

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Genome Research Center for Allergy and Respiratory Diseases, Division of Allergy and Respiratory Medicine, Soonchunhyang University Bucheon Hospital, Bucheon, Republic of Korea.

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.

Show MeSH
Related in: MedlinePlus