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Heterozygous pathogenic variants in POMC are not responsible for monogenic obesity: Implication for MC4R agonist use

dc.rights.licenseopenen_US
dc.contributor.authorLE COLLEN, Lauriane
dc.contributor.authorDELEMER, Brigitte
dc.contributor.authorPOITOU, Christine
dc.contributor.authorVAXILLAIRE, Martine
dc.contributor.authorTOUSSAINT, Bénédicte
dc.contributor.authorDECHAUME, Aurélie
dc.contributor.authorBADREDDINE, Alaa
dc.contributor.authorBOISSEL, Mathilde
dc.contributor.authorDERHOURHI, Mehdi
dc.contributor.authorPETIT, Jean-Michel
dc.contributor.authorTRAN MAU-THEM, Frédéric
dc.contributor.authorBRUEL, Ange-Line
dc.contributor.authorTHAUVIN-ROBINET, Christel
dc.contributor.authorSAVEANU, Alexandru
hal.structure.identifierNeurocentre Magendie : Physiopathologie de la Plasticité Neuronale [U1215 Inserm - UB]
dc.contributor.authorGATTA-CHERIFI, Blandine
dc.contributor.authorLE BEYEC-LE BIHAN, Johanne
dc.contributor.authorFROGUEL, Philippe
dc.contributor.authorBONNEFOND, Amélie
dc.date.accessioned2024-02-28T10:13:01Z
dc.date.available2024-02-28T10:13:01Z
dc.date.issued2023-07
dc.identifier.urihttps://oskar-bordeaux.fr/handle/20.500.12278/188482
dc.description.abstractEnPurpose: Recessive deficiency of proopiomelanocortin (POMC) causes childhood-onset severe obesity. Cases can now benefit from the melanocortin 4 receptor agonist setmelanotide. Furthermore, a phase 3 clinical trial is evaluating setmelanotide in heterozygotes for POMC. We performed a large-scale genetic analysis to assess the effect of heterozygous, pathogenic POMC variants on obesity. Methods: A genetic analysis was performed in a family including 2 cousins with childhood-onset obesity. We analyzed the obesity status of heterozygotes for pathogenic POMC variants in the Human Gene Mutation Database. The association between heterozygous pathogenic POMC variants and obesity risk was assessed using 190,000 exome samples from UK Biobank. Results: The 2 cousins carried a compound heterozygous pathogenic variant in POMC. Six siblings were heterozygotes; only 1 of them had obesity. In Human Gene Mutation Database, we identified 60 heterozygotes for pathogenic POMC variants, of whom 14 had obesity. In UK Biobank, heterozygous pathogenic POMC variants were not associated with obesity risk, but they modestly increased body mass index levels. Conclusion: Heterozygous pathogenic POMC variants do not contribute to monogenic obesity, but they slightly increase body mass index. Setmelanotide use in patients with obesity, which would only be based on the presence of a heterozygous POMC variant, can be questioned. © 2023 American College of Medical Genetics and Genomics
dc.description.sponsorshipEGID Diabetes Pole - ANR-10-LABX-0046en_US
dc.description.sponsorshipPlate forme Lilloise de séquençage du génome humain pour une médecine personnalisée - ANR-10-EQPX-0007en_US
dc.description.sponsorshipPreciDIAB Institute, the holistic approach of personal diabets careen_US
dc.description.sponsorshipOrganisation et montée en puissance d'une Infrastructure Nationale de Génomiqueen_US
dc.language.isoENen_US
dc.subjectHeterozygous
dc.subjectHypocortisolism
dc.subjectObesity
dc.subjectPOMC
dc.subjectVariant
dc.title.enHeterozygous pathogenic variants in POMC are not responsible for monogenic obesity: Implication for MC4R agonist use
dc.title.alternativeGenet Meden_US
dc.typeArticle de revueen_US
dc.identifier.doi10.1016/j.gim.2023.100857en_US
dc.subject.halSciences du Vivant [q-bio]/Neurosciences [q-bio.NC]en_US
dc.identifier.pubmed37092539en_US
dc.description.sponsorshipEuropeEuropean Union (FEDER)en_US
bordeaux.journalGenetics in Medicineen_US
bordeaux.volume25en_US
bordeaux.hal.laboratoriesNeurocentre Magendie - U1215en_US
bordeaux.issue7en_US
bordeaux.institutionUniversité de Bordeauxen_US
bordeaux.institutionINSERMen_US
bordeaux.teamPhysiopathologie de l'équilibre énergétique et obésitéen_US
bordeaux.peerReviewedouien_US
bordeaux.inpressnonen_US
bordeaux.identifier.funderIDConseil Régional Hauts-de-Franceen_US
bordeaux.identifier.funderIDH2020 European Research Councilen_US
hal.identifierhal-04153527
hal.version1
hal.date.transferred2024-02-28T10:13:04Z
hal.popularnonen_US
hal.audienceInternationaleen_US
hal.exporttrue
dc.rights.ccPas de Licence CCen_US
bordeaux.COinSctx_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.jtitle=Genetics%20in%20Medicine&rft.date=2023-07&rft.volume=25&rft.issue=7&rft.au=LE%20COLLEN,%20Lauriane&DELEMER,%20Brigitte&POITOU,%20Christine&VAXILLAIRE,%20Martine&TOUSSAINT,%20B%C3%A9n%C3%A9dicte&rft.genre=article


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