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G protein-coupled r...
G protein-coupled receptor 15 expression is associated with myocardial infarction
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- Haase, Tina (författare)
- University Heart & Vascular Center Hamburg, Department of Cardiology, Hamburg, Germany; German Centre for Cardiovascular Research (DZHK), Partner Site Hamburg, Kiel, Lübeck, Hamburg, Germany
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- Müller, Christian (författare)
- University Heart & Vascular Center Hamburg, Department of Cardiology, Hamburg, Germany; German Centre for Cardiovascular Research (DZHK), Partner Site Hamburg, Kiel, Lübeck, Hamburg, Germany
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- Stoffers, Bastian (författare)
- University Heart & Vascular Center Hamburg, Department of Cardiology, Hamburg, Germany; German Centre for Cardiovascular Research (DZHK), Partner Site Hamburg, Kiel, Lübeck, Hamburg, Germany
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- Kirn, Philipp (författare)
- German Centre for Cardiovascular Research (DZHK), Partner Site Hamburg, Kiel, Lübeck, Hamburg, Germany; Department of Experimental Pharmacology and Toxicology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
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- Waldenberger, Melanie (författare)
- Research Unit Molecular Epidemiology, Helmholtz Zentrum München, Neuherberg, Germany; Institute of Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany; German Centre for Cardiovascular Research (DZHK), Partner Site Munich, Neuherberg, Germany
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- Kaiser, Frank J. (författare)
- Institute of Human Genetics, University Hospital Essen, University Duisburg-Essen, Essen, Germany
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- Karakas, Mahir (författare)
- German Centre for Cardiovascular Research (DZHK), Partner Site Hamburg, Kiel, Lübeck, Hamburg, Germany; Department of Intensive Care Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
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- Kim, Sangwon V. (författare)
- Department of Microbiology and Immunology, Sidney Kimmel Medical College, Thomas Jefferson University, PA, Philadelphia, United States
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- Voss, Svenja (författare)
- University Heart & Vascular Center Hamburg, Department of Cardiology, Hamburg, Germany; German Centre for Cardiovascular Research (DZHK), Partner Site Hamburg, Kiel, Lübeck, Hamburg, Germany
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- Wild, Philipp S. (författare)
- Preventive Cardiology and Preventive Medicine, Department of Cardiology, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany; Center for Thrombosis and Hemostasis, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany; German Centre for Cardiovascular Research (DZHK), Partner Site Rhine-Main, Mainz, Germany
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- Lackner, Karl J. (författare)
- German Centre for Cardiovascular Research (DZHK), Partner Site Rhine-Main, Mainz, Germany; Institute of Clinical Chemistry and Laboratory Medicine, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany
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- Andersson, Jonas, 1977- (författare)
- Umeå universitet,Institutionen för folkhälsa och klinisk medicin
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- Söderberg, Stefan (författare)
- Umeå universitet,Institutionen för folkhälsa och klinisk medicin
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- Lindner, Diana (författare)
- University Heart & Vascular Center Hamburg, Department of Cardiology, Hamburg, Germany; German Centre for Cardiovascular Research (DZHK), Partner Site Hamburg, Kiel, Lübeck, Hamburg, Germany
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- Zeller, Tanja (författare)
- German Centre for Cardiovascular Research (DZHK), Partner Site Hamburg, Kiel, Lübeck, Hamburg, Germany; University Center of Cardiovascular Science, University Heart Vascular Center Hamburg, Hamburg, Germany
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(creator_code:org_t)
- 2022-12-22
- 2023
- Engelska.
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Ingår i: International Journal of Molecular Sciences. - : MDPI. - 1661-6596 .- 1422-0067. ; 24:1
- Relaterad länk:
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https://doi.org/10.3...
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https://umu.diva-por... (primary) (Raw object)
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https://urn.kb.se/re...
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https://doi.org/10.3...
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Abstract
Ämnesord
Stäng
- Beyond the influence of lifestyle-related risk factors for myocardial infarction (MI), the mechanisms of genetic predispositions for MI remain unclear. We sought to identify and characterize differentially expressed genes in early-onset MI in a translational approach. In an observational case–control study, transcriptomes from 112 early-onset MI individuals showed upregulated G protein-coupled receptor 15 (GPR15) expression in peripheral blood mononuclear cells compared to controls (fold change = 1.4, p = 1.87 × 10−7). GPR15 expression correlated with intima-media thickness (β = 0.8498, p = 0.111), C-reactive protein (β = 0.2238, p = 0.0052), ejection fraction (β = −0.9991, p = 0.0281) and smoking (β = 0.7259, p = 2.79 × 10−10). The relation between smoking and MI was diminished after the inclusion of GPR15 expression as mediator in mediation analysis (from 1.27 (p = 1.9 × 10−5) to 0.46 (p = 0.21)). The DNA methylation of two GPR15 sites was 1%/5% lower in early-onset MI individuals versus controls (p = 2.37 × 10−6/p = 0.0123), with site CpG3.98251219 significantly predicting risk for incident MI (hazard ratio = 0.992, p = 0.0177). The nucleotide polymorphism rs2230344 (C/T) within GPR15 was associated with early-onset MI (odds ratio = 3.61, p = 0.044). Experimental validation showed 6.3-fold increased Gpr15 expression in an ischemic mouse model (p < 0.05) and 4-fold increased Gpr15 expression in cardiomyocytes under ischemic stress (p < 0.001). After the induction of MI, Gpr15gfp/gfp mice showed lower survival (p = 0.042) and deregulated gene expression for response to hypoxia and signaling pathways. Using a translational approach, our data provide evidence that GPR15 is linked to cardiovascular diseases, mediating the adverse effects of smoking.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Kardiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cardiac and Cardiovascular Systems (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Medicinsk genetik (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Medical Genetics (hsv//eng)
Nyckelord
- biomarkers
- cardiovascular disease
- epigenetics
- G protein-coupled receptor
- gene expression
- inflammation
- novel molecular target
- pathogenesis
- signal pathway
- translational research
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- ref (ämneskategori)
- art (ämneskategori)
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Haase, Tina
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Müller, Christia ...
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Stoffers, Bastia ...
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Kirn, Philipp
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Waldenberger, Me ...
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Kaiser, Frank J.
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Karakas, Mahir
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Kim, Sangwon V.
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Voss, Svenja
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Wild, Philipp S.
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Lackner, Karl J.
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Andersson, Jonas ...
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Söderberg, Stefa ...
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Lindner, Diana
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Zeller, Tanja
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