Contributors: Epidémiologie des maladies chroniques: impact des intéractions gène environnement sur la santé des populations; Institut Pasteur de Lille; Pasteur Network (Réseau International des Instituts Pasteur)-Pasteur Network (Réseau International des Instituts Pasteur)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire CHU Lille (CHRU Lille); Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC); Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS); CHU Amiens-Picardie; Université de Picardie Jules Verne (UPJV); Centre Hospitalier Régional Universitaire CHU Lille (CHRU Lille); ARC, Fondation De France, and Ligand Pharmaceuticals supported this work. The WHO-MONICA population study developed in the North of France was supported by grants from the Conseil Régional du Nord-Pas de Calais, the Fondation pour la Recherche Médicale, ONIVINS, the Parke-Davis Laboratory, the Mutuelle Générale de l’Education Nationale (MGEN), the Réseau National de Santé Publique, the Direction Générale de La Santé, the Institut National de la Santé Et de la Recherche Médicale (INSERM), the Institut Pasteur de Lille and the Unité d’Evaluation du Center Hospitalier et Universitaire de Lille.; Antonio Vidal-Puig and Giles S.H. Yeo are acknowledged for the lecture of the manuscript and helpful comments. Odile Vidal is acknowledged for plasmid preparation and Xavier Hermant and Valérie Codron for technical assistance.
نبذة مختصرة : International audience ; OBJECTIVE: The peroxisome proliferator-activated receptor-gamma (PPARgamma) plays a role in adipocyte differentiation and insulin sensitization. It has been shown that genetic variation in the PPARgamma gene alters body weight control, lipid and insulin homeostasis, and the susceptibility to type 2 diabetes. Four PPARgamma isoforms are generated by alternative splicing and promoter usage. PPARgamma3 is only expressed in adipose tissue, colon, and macrophages and therefore seems to be a good candidate gene for metabolic and cardiovascular-associated diseases. In the present study, we looked for genetic variation in the PPARgamma3 promoter.METHODS AND RESULTS: The proximal PPARgamma3 promoter was sequenced in 20 individuals. We detected a C/G polymorphism at position -681 from exon A2. Interestingly, it was located in a signal transducer and activator of transcription 5B (STAT5B) binding consensus site. In a French population (n=836), the -681G allele was associated with increased height and plasma low-density lipoprotein cholesterol concentrations. In vitro, we showed that the -681G allele completely abolished the binding of STAT5B to the cognate promoter element as well as the transactivation of the PPARgamma3 promoter by the growth hormone/STAT5B pathway.CONCLUSIONS: Our results suggest that PPARgamma3 may regulate the control of height and lipid homeostasis via the STAT5B pathway.
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