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

Objective— The peroxisome proliferator-activated receptor-γ (PPARγ) plays a role in adipocyte differentiation and insulin sensitization. It has been shown that genetic variation in the PPARγ gene alters body weight control, lipid and insulin homeostasis, and the susceptibility to type 2 diabetes. Four PPARγ isoforms are generated by alternative splicing and promoter usage. PPARγ3 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 PPARγ3 promoter. Methods and Results— The proximal PPARγ3 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...