This evidence includes: (1) the modulation of RAS activity by COMT and 2ME; (2) the role of COMT and 2ME in insulin resistance and the metabolic syndrome; (3) the effects E2 on COMT activity; and (4) the opposite effects of 2ME and E2 on angiogenesis (see Section 7). The gene discussed is COMT; the disease is Insulin resistance.