A Functional Polymorphism in a STAT5B Site of the Human PPARg3 Gene Promoter Affects Height and Lipid Metabolism in a French Population

Objective—The peroxisome proliferator-activated receptor-g (PPARg) plays a role in adipocyte differentiation and insulin sensitization. It has been shown that genetic variation in the PPARg gene alters body weight control, lipid and insulin homeostasis, and the susceptibility to type 2 diabetes. Four PPARg isoforms are generated by alternative splicing and promoter usage. PPARg3 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 PPARg3 promoter. Methods and Results—The proximal PPARg3 promoter was sequenced in 20 individuals. We detected a C/G polymorphism at position 2681 from exon A2. Interestingly, it was located in a signal transducer and activator of transcription 5B (STAT5B) binding consensus site. In a French population (n5836), the 2681G allele was associated with increased height and plasma low-density lipoprotein cholesterol concentrations. In vitro, we showed that the 2681G allele completely abolished the binding of STAT5B to the cognate promoter element as well as the transactivation of the PPARg3 promoter by the growth hormone/STAT5B pathway. Conclusions—Our results suggest that PPARg3 may regulate the control of height and lipid homeostasis via the STAT5B pathway. (Arterioscler Thromb Vasc Biol. 2003;23:●●●-●●●.)