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Exonic variants associated with development of Aspirin Exacerbated Respiratory Diseases

ABSTRACT: Aspirin-exacerbated respiratory disease (AERD) is one phenotype of asthma, often in the form of a severe and sudden attack. Due to time consuming and laborious oral aspirin challenge (OAC) for diagnosis of AERD, non-invasive biomarkers have been searched. Therefore, we scrutinize AERD-associated exonic SNPs and examine the diagnostic potential of combination of these candidate SNPs to predict AERD

ORGANISM(S): Homo sapiens

PROVIDER: GSE61129 | GEO | 2014/09/05

SECONDARY ACCESSION(S): PRJNA260302

REPOSITORIES: GEO

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Exonic variants associated with development of Aspirin Exacerbated Respiratory Diseases

Project description:Aspirin-exacerbated respiratory disease (AERD) is one phenotype of asthma, often in the form of a severe and sudden attack. Due to time consuming and laborious oral aspirin challenge (OAC) for diagnosis of AERD, non-invasive biomarkers have been searched. Therefore, we scrutinize AERD-associated exonic SNPs and examine the diagnostic potential of combination of these candidate SNPs to predict AERD DNA obtained from 164 AERD subjects, 397 subjects with aspirin-tolerant asthma (ATA), 398 normal controls and 10 null samples were subjected to Exome Chip assay of 240K SNPs. 1023 model (210-1) were generated from combination of the top 10 SNPs selected by p-values. The area under the curve (AUC) value of receiver operating characteristic (ROC) curves was calculated for each model. SNP functional Portal and PolyPhen-2 was used to validate the functional significance of the candidate SNPs

2014-09-05 | E-GEOD-61129 | biostudies-arrayexpress

Aspirin Challenge–Induced Genome-Wide DNA Methylation Profile of Peripheral Blood Lymphocytes in Aspirin-Exacerbated Respiratory Disease

Project description:Oral aspirin challenge may induce different global CpG methylation patterns between aspirin-exacerbated respiratory disease (AERD) and aspirin-tolerant asthma (ATA), which may affect gene expression several hours later. Therefore, in the present study, we compared global CpG methylation profiles before and after an oral aspirin challenge in patients with asthma. In addition, we compared differences in methylation profiles between AERD and ATA using an Illumina 860K Infinium Methylation EPIC BeadChip array platform, which had greater coverage than in the previous study (26,485 CpGs) to discover new methylated CpGs in PBLs associated with aspirin-induced bronchospasm.

2023-06-27 | GSE235569 | GEO

Exonic variants associated with development of aspirin exacerbated respiratory diseases.

Project 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 (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.

| S-EPMC4221198 | biostudies-literature

Aspirin Challenge–Induced Genome-Wide DNA Methylation Profile of Peripheral Blood Lymphocytes in Aspirin-Exacerbated Respiratory Disease

Project description:Aspirin Challenge–Induced Genome-Wide DNA Methylation Profile of Peripheral Blood Lymphocytes in Aspirin-Exacerbated Respiratory Disease

| PRJNA986480 | ENA

Half-lives of aspirin-mediated lysine acetylations

Project description:Aspirin, or acetylsalicylic acid is widely used to control pain, inflammation and fever. An important property of aspirin is its ability to acetylate multiple cellular proteins with some pharmacological functions explicable by the irreversible acetylation of cyclooxygenases at active site serine residues. We have used a labeled form of aspirin, aspirin-d3 to acetylate proteins in cultured human cells, and unambiguously identified over 12000 sites of acetylation, using acetylated lysine peptide enrichment combined with mass-spectrometry-based proteomics. Aspirin increases lysine acetylation occupancy of the majority of detected endogenous sites, but leaves almost unchanged a small group that are already highly acetylated. We show that cells are remarkably tolerant of this acetylation insult unless endogenous deacetylases are inhibited. This work raises the possibility that rather than single protein effects, some of the clinical features of aspirin may be the consequence of multiple concurrent protein modifications, and that combining aspirin with lysine deacetylase inhibitors may have important medical implications.

2019-03-05 | PXD003655 | Pride

Sites of aspirin-mediated lysine acetylation in HeLa cells

Project description:Aspirin, or acetylsalicylic acid is widely used to control pain, inflammation and fever. Important to this function is its ability to irreversibly acetylate cyclooxygenases at active site serines. Aspirin has the potential to acetylate other amino-acid side-chains, leading to speculation that aspirin-mediated lysine acetylation could explain some of its drug actions or side-effects. Using a labeled form of aspirin, aspirin-d3, we identified over 12000 sites of lysine acetylation from cultured human cells. Although aspirin amplifies acetylation signals at thousands of sites, cells tolerate aspirin mediated acetylation very well unless endogenous deacetylases are inhibited. Apart from a limited number of cellular proteins that are substantially acetylated under endogenous conditions, aspirin mediated acetylation leads to a large increase in the acetylation of many proteins even although they remain at very low stoichiometry. This reinforces the idea that a major function of cellular deacetylases is the suppression of non-specific or non-enzymatic protein acetylation.

2017-01-10 | PXD003530 | Pride

STOX1 placenta w/o aspirin

Project description:STOX1 overexpressing placentas generate preeclampsia-like symptoms in pregnant mice. These symptoms are reverted by aspirin. The experiment aims at analyzing placental expression in Transgenic/non transgenic with and withou aspirin, in the placentas at 16,5 days post-coïtum. There are two strains of transgenic mice that express the transgene at different levels: STOX42 about 15 fold that of STOX13. STOX13 expressed the human STOX1 roughly at the level of the mouse endogeneous Stox1 in the placenta.

2013-10-11 | E-MTAB-1970 | biostudies-arrayexpress

Novel single nucleotide polymorphism markers for low dose aspirin-associated small bowel bleeding

Project description:Blood from 17 patients taking enteric-coated low-dose aspirin (LDA) and with suspected bleeding from small intestine and 18 control patients taking aspirin were analyzed. Results provide insight into the risk for aspirin-induced small bowel bleeding.

2013-11-08 | GSE52155 | GEO

Aspirin antitumoral effect on pituitary adenoma

Project description:Aspirin, is a commonly used non-steroidal anti-inflammatory drug with antipyretic, analgesic, anti-inflammatory, and anti-thrombotic effect. Its antitumoral effect was also demonstrated in several cancer types. In this study our aim was to investigate the genomic effects of ASA in pituitary adenomas using high-throughput profiling approaches and validate our findings by targeted methodologies, using in vitro functional assays. Whole transcriptome profile of RC4-B/C and GH3 pituitary cell lines upon Aspirin treatment was investigated.

2022-06-19 | GSE202934 | GEO

Placental Effects of Aspirin treatment in preeclamptic women

Project description:Aspirin is currently the only drug used in preeclampsia, a major hypertensive disorder of pregnancy. The counselled doses are low (75-150 mg/day), and the actual effects of aspirin are not well understood, especially in the target organ, the placenta.This is the aim of the present study.

2022-12-31 | E-MTAB-12434 | biostudies-arrayexpress

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