Glucose-dependent regulation of NR2F2 promoter and influence of SNP-rs3743462 on whole body insulin sensitivity.

摘要: Background The Nuclear Receptor 2F2 (NR2F2/COUP-TFII) heterozygous knockout mice display low basal insulinemia and enhanced insulin sensitivity. We previously established that represses NR2F2 gene expression in pancreatic β-cells. The cis-regulatory region of the promoter is unknown its influence on metabolism humans poorly understood. present study aimed to identify regulatory regions control transcription evaluate effect variation glucose homeostasis humans. Methodology/Principal Findings Regulation was assessed using reporter assays, ChIP gel shift experiments. effects at SNP rs3743462 quantitative metabolic traits were studied two European prospective cohorts. identified a minimal down-regulates by attenuating HNF4α activation response high concentrations. Subjects French DESIR population, who carried T-to-C polymorphism, located distal glucose-responsive promoter, displayed lower levels HOMA-IR index. C-allele associated with increased binding decreased expression. Conclusions/Significance polymorphism affects regulation thereby may whole-body sensitivity, suggesting role humans.