A Functional Polymorphism in a STAT5B Site of the Human PPARγ3 Gene Promoter Affects Height and Lipid Metabolism in a French Population

Aline Meirhaeghe (1) , Lluis Fajas (2) , Fabrice Gouilleux (3, 4) , Dominique Cottel (1) , Nicole Helbecque (1) , Johan Auwerx (2) , Philippe Amouyel (1, 5)

1 Epidémiologie des maladies chroniques: impact des intéractions gène environnement sur la santé des populations
2 IGBMC - Institut de Génétique et de Biologie Moléculaire et Cellulaire
3 CHU Amiens-Picardie
4 UPJV - Université de Picardie Jules Verne
5 CHRU Lille - Centre Hospitalier Régional Universitaire [Lille]

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.

Keywords: growth hormone; obesity; cholesterol; STAT; PPAR; growth hormone

Domains: Life Sciences [q-bio]

Aline Meirhaeghe, Lluis Fajas, Fabrice Gouilleux, Dominique Cottel, Nicole Helbecque, et al.. A Functional Polymorphism in a STAT5B Site of the Human PPARγ3 Gene Promoter Affects Height and Lipid Metabolism in a French Population. Arteriosclerosis, Thrombosis, and Vascular Biology, 2003, 23 (2), pp.289-294. ⟨10.1161/01.atv.0000051382.28752.fe⟩. ⟨hal-02427352⟩