title: A functional polymorphism in a STAT5B site of the human PPAR gamma 3 gene promoter affects height and lipid metabolism in a French population.
abstract: 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.
  
  
  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.
authors.affiliation: Service d'Epidémiologie et de Santé Publique, INSERM U.508, Institut Pasteur de Lille, France.
authors.forename: Aline
authors.initials: A
authors.lastname: Meirhaeghe
authors.forename: Lluis
authors.initials: L
authors.lastname: Fajas
authors.forename: Fabrice
authors.initials: F
authors.lastname: Gouilleux
authors.forename: Dominique
authors.initials: D
authors.lastname: Cottel
authors.forename: Nicole
authors.initials: N
authors.lastname: Helbecque
authors.forename: Johan
authors.initials: J
authors.lastname: Auwerx
authors.forename: Philippe
authors.initials: P
authors.lastname: Amouyel
mesh_terms: D000328:Adult; D001827:Body Height / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000502:physiology; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D006801:Humans; D015810:Linkage Disequilibrium / Q000235:genetics; D008052:Lipid Metabolism, Inborn Errors / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D008894:Milk Proteins; D008969:Molecular Sequence Data; D011110:Polymorphism, Genetic / Q000502:physiology*; D011401:Promoter Regions, Genetic / Q000502:physiology*; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics* / Q000502:physiology; D050799:STAT5 Transcription Factor; D015534:Trans-Activators / Q000235:genetics* / Q000502:physiology; D014157:Transcription Factors / Q000235:genetics* / Q000502:physiology
chemical_list: D004268:DNA-Binding Proteins; D008894:Milk Proteins; D018160:Receptors, Cytoplasmic and Nuclear; D050799:STAT5 Transcription Factor; C494095:STAT5B protein, human; D015534:Trans-Activators; D014157:Transcription Factors