| Domaine : |
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Sciences du Vivant/Génétique/Génétique humaine
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PMID (identifiant
de la référence Pubmed) : |
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 (17519222) |
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| Titre : |
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Non-synonymous polymorphisms in melanocortin-4 receptor protect against obesity: the two facets of a Janus obesity gene. |
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| Auteur(s) : |
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Fanny Stutzmann, Vincent Vatin1, Stéphane Cauchi1, Anita Morandi, Béatrice Jouret, Olfert Landt, Patrick Tounian, Claire Levy-Marchal, Raffaella Buzzetti, Leonardo Pinelli, Beverley Balkau2, 3, Fritz Horber4, Pierre Bougnères, Philippe Froguel1, 5, 6, David Meyre1 |
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| Laboratoire : |
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| 1 : |
GMM - Génétique des maladies multifactorielles |
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| http://www-good.pasteur-lille.fr |
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| CNRS : UMR8090 – Université Lille II - Droit et santé |
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| 1 Rue du professeur Calmette - BP 245 59019 LILLE CEDEX |
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| France |
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| 2 : |
Recherche en épidémiologie et biostatistique |
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| INSERM : IFR69 – Université Paris XI - Paris Sud |
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| 16, Avenue Paul Vaillant-Couturier 94807 VILLEJUIF CEDEX |
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| France |
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| 3 : |
Epidémiologie cardiovasculaire et métabolique |
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| INSERM : IFR69 – Université Paris XI - Paris Sud |
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| Hôpital Paul Brousse 16, Avenue Paul Vaillant-Couturier 94807 VILLEJUIF CEDEX |
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| France |
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| 4 : |
Dr. Horber Adipositas Stiftung |
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| Dr. Horber Adipositas Stiftung |
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| Hornbachstrasse 50, 8034, Zürich |
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| Suisse |
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| 5 : |
Section of Genomic Medicine |
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| Imperial College |
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| W2 0NN London |
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| Royaume-Uni |
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| 6 : |
Genome Centre |
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| http://www.smd.qmul.ac.uk/gc/ |
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| Imperial College London – Hammersmith campus |
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| John Vane Science Centre, Queen Mary, University of London, Charterhouse Square, London EC1M 6BQ, Tel: +44 (0)20 7882 2055, Fax: +44 (0)20 7882 8406 |
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| Royaume-Uni |
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| Résumé : |
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The melanocortin-4 receptor (MC4R) gene pathogenic mutations are the most prevalent forms of monogenic obesity, responsible for approximately 2% of obesity cases, but its role in common obesity is still elusive. We analyzed the contribution of non-synonymous mutations V103I (rs2229616, c.307G > A) and I251L (no rs, c.751A > C) to obesity in 16 797 individuals of European origin from nine independent case-control, population-based and familial cohorts. We observed a consistent negative association of I251L variant (prevalence ranging 0.41-1.21%) with both childhood and adult class III obesity [odds ratio (OR) ranging from 0.25 to 0.76, 0.001 < P-value < 0.05] and with modulation of body mass index (BMI) in general populations, in eight out of nine studies, whereas only one study showed an association between V103I and BMI. Meta-analyses of previous published data with the current ones provided strong evidence of the protective effect of I251L toward obesity (OR = 0.52, P = 3.58 10-5), together with a modest negative association between V103I and obesity (OR = 0.80, P = 0.002). Taken together, gain-of-function mutations I251L and V103I may be responsible for a preventive fraction of obesity of 2%, which mirrors the prevalence of monogenic obesity due to MC4R haploinsufficiency. These results also emphasize the importance of the MC4R signalling tonus to prevent obesity, even in the context of our current obesogenic environment. |
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Langue du texte
intégral : |
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Anglais |
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| Type de publication : |
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Articles dans des revues avec comité de lecture |
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| DOI : |
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10.1093/hmg/ddm132 |
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| Journal : |
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| Human Molecular Genetics (Hum Mol Genet) |
| Publisher |
Oxford University Press (OUP): Policy B - Oxford Open Option B |
| ISSN |
0964-6906 (eISSN : 1460-2083) |
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| Audience : |
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non spécifiée |
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| Date de publication : |
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01/08/2007 |
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Date de publication
électronique : |
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21/05/2007 |
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| Volume : |
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16 |
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| Numéro : |
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15 |
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| Page, identifiant, ... : |
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1837-44 |
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