IR can cause NO reduction and vasoconstrictor endothelin-1 (ET-1) increase involving in the phosphatidylinositol 3-kinase (PI3K) and mitogen-activated protein kinase (MAPK) signalling pathways, which in turn impairs endothelial cell function and enhances platelet adhesion, activation and aggregation, leading to thrombosis and increased stroke risk (30, 31). The gene discussed is WNK2; the disease is Stroke.