Novel single nucleotide polymorphism markers for low dose aspirin-associated small bowel bleeding
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE52155 | GEO | 2013/11/08
SECONDARY ACCESSION(S): PRJNA227145
REPOSITORIES: GEO
Similar Datasets
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. 35 samples; 1 array per sample.
2013-11-08 | E-GEOD-52155 | biostudies-arrayexpress
Project description:The risk of bleeding after polypectomy of large colorectal polyps in patients taking aspirin is uncertain. This is a randomized, multi-center, placebo-controlled, double-blind study to compare the risk of significant bleeding after endoscopic polypectomy of large (>=10mm) colorectal polyps in patients continuing or discontinuing on daily acetylsalicylic acid (ASA) use. Eligible patients will be randomly assigned in a 1:1 ratio to a group taking 75mg daily ASA or placebo 7 days before and 14 days following polypectomy. The primary endpoint of the study is bleeding within 30 days from colorectal polypectomy. The secondary endpoints are composite cardiovascular events occurring between the date of randomization and 30 days after polypectomy.
| 2121606 | ecrin-mdr-crc
Project description:BackgroundAspirin-induced enteropathy is now increasingly being recognized although the pathogenesis of small intestinal damage induced by aspirin is not well understood and related risk factors have not been established.AimTo investigate pharmacogenomic profile of low dose aspirin (LDA)-induced small bowel bleeding.MethodsGenome-wide analysis of single nucleotide polymorphisms (SNPs) was performed using the Affymetrix DMET™ Plus Premier Pack. Genotypes of candidate genes associated with small bowel bleeding were determined using TaqMan SNP Genotyping Assay kits and direct sequencing.ResultsIn the validation study in overall 37 patients with small bowel bleeding and 400 controls, 4 of 27 identified SNPs: CYP4F11 (rs1060463) GG (p=0.003), CYP2D6 (rs28360521) GG (p=0.02), CYP24A1 (rs4809957) T allele (p=0.04), and GSTP1 (rs1695) G allele (p=0.04) were significantly more frequent in the small bowel bleeding group compared to the controls. After adjustment for significant factors, CYP2D6 (rs28360521) GG (OR 4.11, 95% CI. 1.62 -10.4) was associated with small bowel bleeding.ConclusionsCYP4F11 and CYP2D6 SNPs may identify patients at increased risk for aspirin-induced small bowel bleeding.
| S-EPMC3867469 | biostudies-literature
Project description:Atrial fibrillation (AF) is a major risk factor for cardioembolic stroke. Anticoagulant drugs are effective in preventing AF-related stroke. However, the high frequency of anticoagulant-associated major bleeding is a major concern particularly when antiplatelet treatment is simultaneously administered. Here, microarray analysis in peripheral blood cells in eight patients with AF and stroke and eight AF subjects without stroke identified a stroke related gene expression pattern. HSPA1B, which encodes for heat-shock protein 70 kDa (Hsp70), was the most differentially expressed gene. This gene was downregulated in stroke subjects, a finding confirmed further in an independent AF cohort of 200 individuals. Hsp70 knock-out (KO) mice subjected to different thrombotic challenges developed thrombosis significantly earlier than their wild-type (WT) counterparts. In WT mice, Hsp70 inducers (TRC051384, or tubastatin A) delayed thrombus formation. Remarkably, Hsp70 inducers did not increase the bleeding risk even when aspirin was concomitantly administered. Hsp70 induction was associated with an increased vascular thrombomodulin expression, higher circulating levels of activated protein C (APC) upon thrombotic stimulus and increased protection against endothelial apoptosis. Thus, Hsp70 induction is a novel approach to delay thrombus formation with minimal bleeding risk, being especially promising in situations where there is a major bleeding hazard. Microarray analysis in peripheral blood cells includes eight patients with AF and stroke and eight AF subjects without stroke
2016-04-01 | E-GEOD-66724 | biostudies-arrayexpress
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
Project description:Atrial fibrillation (AF) is a major risk factor for cardioembolic stroke. Anticoagulant drugs are effective in preventing AF-related stroke. However, the high frequency of anticoagulant-associated major bleeding is a major concern particularly when antiplatelet treatment is simultaneously administered. Here, microarray analysis in peripheral blood cells in eight patients with AF and stroke and eight AF subjects without stroke identified a stroke related gene expression pattern. HSPA1B, which encodes for heat-shock protein 70 kDa (Hsp70), was the most differentially expressed gene. This gene was downregulated in stroke subjects, a finding confirmed further in an independent AF cohort of 200 individuals. Hsp70 knock-out (KO) mice subjected to different thrombotic challenges developed thrombosis significantly earlier than their wild-type (WT) counterparts. In WT mice, Hsp70 inducers (TRC051384, or tubastatin A) delayed thrombus formation. Remarkably, Hsp70 inducers did not increase the bleeding risk even when aspirin was concomitantly administered. Hsp70 induction was associated with an increased vascular thrombomodulin expression, higher circulating levels of activated protein C (APC) upon thrombotic stimulus and increased protection against endothelial apoptosis. Thus, Hsp70 induction is a novel approach to delay thrombus formation with minimal bleeding risk, being especially promising in situations where there is a major bleeding hazard.
2016-04-01 | GSE66724 | GEO
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
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
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
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