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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2003;23:289.)
© 2003 American Heart Association, Inc.

Atherosclerosis and Lipoproteins

A Functional Polymorphism in a STAT5B Site of the Human PPAR3 Gene Promoter Affects Height and Lipid Metabolism in a French Population

Aline Meirhaeghe; Lluis Fajas; Fabrice Gouilleux; Dominique Cottel; Nicole Helbecque; Johan Auwerx; Philippe Amouyel

From the Service d’Epidémiologie et de Santé Publique, INSERM U.508 (A.M., D.C., N.H., P.A.), Institut Pasteur de Lille; IGBMC (L.F., J.A.), Illkirch; Faculté de Médecine (F.G.), CHU d’Amiens, Amiens Cedex; and Centre Hospitalier et Universitaire de Lille (P.A.), Lille, France.

Correspondence to Pr. Philippe Amouyel, Service d’Epidémiologie et de Santé Publique, INSERM U.508, Institut Pasteur de Lille, 1 rue Calmette, BP 245, 59019 Lille Cedex, France. E-mail Philippe.Amouyel{at}pasteur-lille.fr

Objective— The peroxisome proliferator-activated receptor- (PPAR) plays a role in adipocyte differentiation and insulin sensitization. It has been shown that genetic variation in the PPAR gene alters body weight control, lipid and insulin homeostasis, and the susceptibility to type 2 diabetes. Four PPAR isoforms are generated by alternative splicing and promoter usage. PPAR3 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 PPAR3 promoter.

Methods and Results— The proximal PPAR3 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 PPAR3 promoter by the growth hormone/STAT5B pathway.

Conclusions— Our results suggest that PPAR3 may regulate the control of height and lipid homeostasis via the STAT5B pathway.

Key Words: obesity • cholesterol • PPAR • growth hormone • STAT

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