First of all, the defects downstream of insulin receptor phosphorylation, such as activation of phosphorylated IRS-1 through PKC or GLUT-4 translocation through PI3K/Akt signaling pathway, are the causes of IR in some PCOS women.41,339 Second, certain proinflammatory mediators including TNF, C-reactive protein (CRP), monocyte chemoattractant protein-1 (MCP-1) and IL-18 levels are elevated in PCOS women independently of obesity.340–342 Furthermore, hyperglycemia may contribute to inflammation in PCOS, possibly by inducing oxidative stress via increased ROS production. The gene discussed is CRP; the disease is obesity due to melanocortin 4 receptor deficiency.