There are multiple causes for endothelial uncoupling in addition to hyperuricemia and the antioxidant – prooxidant urate redox shuttle: A-FLIGHT -U toxicities, ROS, T2DM, prediabetes, T1DM, insulin resistance, MS, renin angiotensin aldosterone activation, angiotensin II, hypertension, endothelin, dyslipidemia – hyperlipidemia, homocysteine, and asymmetrical dimethyl arginine (ADMA) [19,39,43]. The gene discussed is REN; the disease is hypertensive disorder.