Untargeted Metabolomics Profiling Reveals Perturbations in Arginine-NO Metabolism in Middle Eastern Patients with Coronary Heart Disease

<p dir="ltr">Coronary heart disease (CHD) is a major cause of death in Middle Eastern (ME) populations, with current studies of the metabolic fingerprints of CHD lacking in diversity. Identification of specific biomarkers to uncover potential mechanisms for developing predictive mode...

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محفوظ في:
التفاصيل البيبلوغرافية
المؤلف الرئيسي: Ehsan Ullah (2698921) (author)
مؤلفون آخرون: Ayman El-Menyar (440103) (author), Khalid Kunji (828224) (author), Reem Elsousy (18372435) (author), Haira R. B. Mokhtar (18372438) (author), Eiman Ahmad (18372441) (author), Maryam Al-Nesf (5712296) (author), Alka Beotra (14780368) (author), Mohammed Al-Maadheed (12204886) (author), Vidya Mohamed-Ali (12204895) (author), Mohamad Saad (214545) (author), Jassim Al Suwaidi (284932) (author)
منشور في: 2022
الموضوعات:
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author Ehsan Ullah (2698921)
author2 Ayman El-Menyar (440103)
Khalid Kunji (828224)
Reem Elsousy (18372435)
Haira R. B. Mokhtar (18372438)
Eiman Ahmad (18372441)
Maryam Al-Nesf (5712296)
Alka Beotra (14780368)
Mohammed Al-Maadheed (12204886)
Vidya Mohamed-Ali (12204895)
Mohamad Saad (214545)
Jassim Al Suwaidi (284932)
author2_role author
author
author
author
author
author
author
author
author
author
author
author_facet Ehsan Ullah (2698921)
Ayman El-Menyar (440103)
Khalid Kunji (828224)
Reem Elsousy (18372435)
Haira R. B. Mokhtar (18372438)
Eiman Ahmad (18372441)
Maryam Al-Nesf (5712296)
Alka Beotra (14780368)
Mohammed Al-Maadheed (12204886)
Vidya Mohamed-Ali (12204895)
Mohamad Saad (214545)
Jassim Al Suwaidi (284932)
author_role author
dc.creator.none.fl_str_mv Ehsan Ullah (2698921)
Ayman El-Menyar (440103)
Khalid Kunji (828224)
Reem Elsousy (18372435)
Haira R. B. Mokhtar (18372438)
Eiman Ahmad (18372441)
Maryam Al-Nesf (5712296)
Alka Beotra (14780368)
Mohammed Al-Maadheed (12204886)
Vidya Mohamed-Ali (12204895)
Mohamad Saad (214545)
Jassim Al Suwaidi (284932)
dc.date.none.fl_str_mv 2022-06-03T03:00:00Z
dc.identifier.none.fl_str_mv 10.3390/metabo12060517
dc.relation.none.fl_str_mv https://figshare.com/articles/journal_contribution/Untargeted_Metabolomics_Profiling_Reveals_Perturbations_in_Arginine-NO_Metabolism_in_Middle_Eastern_Patients_with_Coronary_Heart_Disease/25609449
dc.rights.none.fl_str_mv CC BY 4.0
info:eu-repo/semantics/openAccess
dc.subject.none.fl_str_mv Biomedical and clinical sciences
Cardiovascular medicine and haematology
Medical biochemistry and metabolomics
metabolomics
coronary heart disease
arginine metabolism
metabolite risk score
Middle East
dc.title.none.fl_str_mv Untargeted Metabolomics Profiling Reveals Perturbations in Arginine-NO Metabolism in Middle Eastern Patients with Coronary Heart Disease
dc.type.none.fl_str_mv Text
Journal contribution
info:eu-repo/semantics/publishedVersion
text
contribution to journal
description <p dir="ltr">Coronary heart disease (CHD) is a major cause of death in Middle Eastern (ME) populations, with current studies of the metabolic fingerprints of CHD lacking in diversity. Identification of specific biomarkers to uncover potential mechanisms for developing predictive models and targeted therapies for CHD is urgently needed for the least-studied ME populations. A case-control study was carried out in a cohort of 1001 CHD patients and 2999 controls. Untargeted metabolomics was used, generating 1159 metabolites. Univariate and pathway enrichment analyses were performed to understand functional changes in CHD. A metabolite risk score (MRS) was developed to assess the predictive performance of CHD using multivariate analysis and machine learning. A total of 511 metabolites were significantly different between the CHD patients and the controls (FDR p < 0.05). The enriched pathways (FDR p < 10−300) included D-arginine and D-ornithine metabolism, glycolysis, oxidation and degradation of branched chain fatty acids, and sphingolipid metabolism. MRS showed good discriminative power between the CHD cases and the controls (AUC = 0.99). In this first study in the Middle East, known and novel circulating metabolites and metabolic pathways associated with CHD were identified. A small panel of metabolites can efficiently discriminate CHD cases and controls and therefore can be used as a diagnostic/predictive tool.</p><h2>Other Information</h2><p dir="ltr">Published in: Metabolites<br>License: <a href="https://creativecommons.org/licenses/by/4.0/" target="_blank">https://creativecommons.org/licenses/by/4.0/</a><br>See article on publisher's website: <a href="https://dx.doi.org/10.3390/metabo12060517" target="_blank">https://dx.doi.org/10.3390/metabo12060517</a></p>
eu_rights_str_mv openAccess
id Manara2_e2bf70c7d1de32bae714347840da8512
identifier_str_mv 10.3390/metabo12060517
network_acronym_str Manara2
network_name_str Manara2
oai_identifier_str oai:figshare.com:article/25609449
publishDate 2022
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rights_invalid_str_mv CC BY 4.0
spelling Untargeted Metabolomics Profiling Reveals Perturbations in Arginine-NO Metabolism in Middle Eastern Patients with Coronary Heart DiseaseEhsan Ullah (2698921)Ayman El-Menyar (440103)Khalid Kunji (828224)Reem Elsousy (18372435)Haira R. B. Mokhtar (18372438)Eiman Ahmad (18372441)Maryam Al-Nesf (5712296)Alka Beotra (14780368)Mohammed Al-Maadheed (12204886)Vidya Mohamed-Ali (12204895)Mohamad Saad (214545)Jassim Al Suwaidi (284932)Biomedical and clinical sciencesCardiovascular medicine and haematologyMedical biochemistry and metabolomicsmetabolomicscoronary heart diseasearginine metabolismmetabolite risk scoreMiddle East<p dir="ltr">Coronary heart disease (CHD) is a major cause of death in Middle Eastern (ME) populations, with current studies of the metabolic fingerprints of CHD lacking in diversity. Identification of specific biomarkers to uncover potential mechanisms for developing predictive models and targeted therapies for CHD is urgently needed for the least-studied ME populations. A case-control study was carried out in a cohort of 1001 CHD patients and 2999 controls. Untargeted metabolomics was used, generating 1159 metabolites. Univariate and pathway enrichment analyses were performed to understand functional changes in CHD. A metabolite risk score (MRS) was developed to assess the predictive performance of CHD using multivariate analysis and machine learning. A total of 511 metabolites were significantly different between the CHD patients and the controls (FDR p < 0.05). The enriched pathways (FDR p < 10−300) included D-arginine and D-ornithine metabolism, glycolysis, oxidation and degradation of branched chain fatty acids, and sphingolipid metabolism. MRS showed good discriminative power between the CHD cases and the controls (AUC = 0.99). In this first study in the Middle East, known and novel circulating metabolites and metabolic pathways associated with CHD were identified. A small panel of metabolites can efficiently discriminate CHD cases and controls and therefore can be used as a diagnostic/predictive tool.</p><h2>Other Information</h2><p dir="ltr">Published in: Metabolites<br>License: <a href="https://creativecommons.org/licenses/by/4.0/" target="_blank">https://creativecommons.org/licenses/by/4.0/</a><br>See article on publisher's website: <a href="https://dx.doi.org/10.3390/metabo12060517" target="_blank">https://dx.doi.org/10.3390/metabo12060517</a></p>2022-06-03T03:00:00ZTextJournal contributioninfo:eu-repo/semantics/publishedVersiontextcontribution to journal10.3390/metabo12060517https://figshare.com/articles/journal_contribution/Untargeted_Metabolomics_Profiling_Reveals_Perturbations_in_Arginine-NO_Metabolism_in_Middle_Eastern_Patients_with_Coronary_Heart_Disease/25609449CC BY 4.0info:eu-repo/semantics/openAccessoai:figshare.com:article/256094492022-06-03T03:00:00Z
spellingShingle Untargeted Metabolomics Profiling Reveals Perturbations in Arginine-NO Metabolism in Middle Eastern Patients with Coronary Heart Disease
Ehsan Ullah (2698921)
Biomedical and clinical sciences
Cardiovascular medicine and haematology
Medical biochemistry and metabolomics
metabolomics
coronary heart disease
arginine metabolism
metabolite risk score
Middle East
status_str publishedVersion
title Untargeted Metabolomics Profiling Reveals Perturbations in Arginine-NO Metabolism in Middle Eastern Patients with Coronary Heart Disease
title_full Untargeted Metabolomics Profiling Reveals Perturbations in Arginine-NO Metabolism in Middle Eastern Patients with Coronary Heart Disease
title_fullStr Untargeted Metabolomics Profiling Reveals Perturbations in Arginine-NO Metabolism in Middle Eastern Patients with Coronary Heart Disease
title_full_unstemmed Untargeted Metabolomics Profiling Reveals Perturbations in Arginine-NO Metabolism in Middle Eastern Patients with Coronary Heart Disease
title_short Untargeted Metabolomics Profiling Reveals Perturbations in Arginine-NO Metabolism in Middle Eastern Patients with Coronary Heart Disease
title_sort Untargeted Metabolomics Profiling Reveals Perturbations in Arginine-NO Metabolism in Middle Eastern Patients with Coronary Heart Disease
topic Biomedical and clinical sciences
Cardiovascular medicine and haematology
Medical biochemistry and metabolomics
metabolomics
coronary heart disease
arginine metabolism
metabolite risk score
Middle East