A Pro12Ala substitution in PPARgamma2 associated with decreased receptor activity, lower body mass index and improved insulin sensitivity.

摘要: The peroxisome proliferator-activated receptor-gamma (PPARgamma) is a transcription factor that has pivotal role in adipocyte differentiation and expression of adipocyte-specific genes. PPARgamma1 gamma2 isoforms result from alternative splicing have ligand-dependent -independent activation domains. PPARgamma2 an additional 28 amino acids at its terminus renders ligand-independent domain 5-10-fold more effective than PPARgamma1. Insulin stimulates the (ref. 5), however, obesity nutritional factors only influence human adipocytes. Here, we report relatively common Pro12Ala substitution associated with lower body mass index (BMI; P=0.027; 0.015) improved insulin sensitivity among middle-aged elderly Finns. A significant odds ratio (4.35, P=0.028) for association Pro/Pro genotype type 2 diabetes was observed Japanese Americans. Ala allele showed decreased binding affinity to cognate promoter element reduced ability transactivate responsive promoters. These findings suggest variant may contribute variability BMI general population.