In the periphery, APOE2 is associated with decreased low-density lipoprotein (LDL) cholesterol, whereas APOE4 is associated with increased LDL cholesterol, relative to APOE3. While this may account for APOE association with cardiovascular disease, the mechanisms underlying APOE allelic effects on glucose metabolism, inflammation and innate immunity are less clear2. The gene discussed is APOE; the disease is cardiovascular disorder.