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pmid:34611404
Bioinformatics Analysis of a Functional ANGPT1 Variant That Interferes with miR-607 and Its Association with Susceptibility and Outcome of Ischemic Stroke in a Han Population.
Ai-Nian Chen · Ling-Ling Zhong · Ke-Ju Ju · Hua Cao
Therapeutics and clinical risk management · 2021 doi:10.2147/TCRM.S328964
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Complete file
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We used bioinformatics approaches to investigate a functional ANGPT1 variant that interferes with miR-607 and explored its association with IS.\nMATERIALS AND METHODS: An IS expression microarray (GSE16561) was downloaded from the GEO and used to identify differentially expressed genes (DEGs) and functional enrichment pathways. Analyses showed that ANGPT1 participated in six key pathways and was susceptible to a key functional polymorphism rs2507799. We genotyped 567 IS patients and 500 controls for ANGPT1 rs2507799. Luciferase assays were also conducted to investigate the binding between miR-607 and ANGPT1 rs2507799.\nRESULTS: In total, we identified 458 DEGs between IS patients and healthy controls in the GSE16561 dataset. GO functional enrichment analysis showed that these DEGs were mainly enriched in cell-substrate junctions, the regulation of peptide secretion, and the regulation of cytokine secretion involved in immune response. ANGPT1 rs2507799 T-carriers had a significantly higher risk of IS (Dominant model: OR = 1.48, 95% CI = 1.01-2.17, P = 0.044). IS patients harboring the TC/TT genotype experienced significantly more severe injuries in terms of neurological function (Dominant model: OR = 2.06, 95% CI = 1.28-3.31, P = 0.003). Analysis also showed that IS patients harboring the TC/TT genotype had a significantly worse outcome (Dominant model: OR = 2.22, 95% CI = 1.35-3.67, P = 0.002). Luciferase assays indicated that miR-607 could affect luciferase activity by binding to the ANGPT1 mutant type.\nCONCLUSION: In this study, we used bioinformatical methods to investigate a key IS-related gene ANGPT1 and its functional polymorphism rs2507799. rs2507799 was found to be associated with a significantly increased risk for IS, a significantly more severe initial stroke severity, and a worse outcome. These results may help to improve the future management of ischemic stroke.", "claims": [{"id": "claim-method", "statement": "The relationships between genotypes and IS susceptibility, severity, and functional outcome, were estimated by odds ratios (ORs) and 95% confidence intervals (CIs) using multivariate logistic regression analysis.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:34611404", "locator": "sections[10] \"Statistical Analysis\" paragraph 2", "quote": "The relationships between genotypes and IS susceptibility, severity, and functional outcome, were estimated by odds ratios (ORs) and 95% confidence intervals (CIs) using multivariate logistic regression analysis."}], "state": "complete"}, {"id": "claim-data-access", "statement": "We downloaded a matrix file (GSE16561) from the GEO that contained IS expression profile data.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:34611404", "locator": "sections[1] \"Introduction\" paragraph 4", "quote": "We downloaded a matrix file (GSE16561) from the GEO that contained IS expression profile data."}], "state": "complete"}, {"id": "claim-target-result", "statement": "ANGPT1 rs2507799 was found to be associated with a significantly increased risk for IS, a significantly more severe initial stroke severity, and a worse outcome.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:34611404", "locator": "sections[0] \"Abstract\" paragraph 4", "quote": "rs2507799 was found to be associated with a significantly increased risk for IS, a significantly more severe initial stroke severity, and a worse outcome."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "ANGPT1 rs2507799 was found to be associated with a significantly increased risk for IS, a significantly more severe initial stroke severity, and a worse outcome.", "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:34611404"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "complete", "blocked_on": null, "description": "The GEO series accession resolves and its sample accessions are listed. This lane did not download the dataset or read its licence.", "duration_hours": null, "parameters": {}, "inputs": ["data:geo:GSE16561"], "outputs": ["the source data with its repository provenance"], "instruments": [], "reagents": []}, {"id": "run_analysis", "order": 3, "name": "Run the published analysis", "kind": "analysis", "state": "complete", "blocked_on": null, "description": "Apply the paper's statistical method to the resolved series and compare the result with the published target.", "duration_hours": null, "parameters": {}, "inputs": ["data:geo:GSE16561"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:34611404", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.2147/TCRM.S328964", "sha256": "sha256:43c05e9ff642079644c854407712e939213c929ba85da021ce255b43bd3b2fa0", "bytes": 22731, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.2147/TCRM.S328964", "version": null, "note": "Full article fetched from PMC; 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