All studies have demonstrated a strong association between plasma cholesterol and apoE phenotypes in the following order: E4/E4 > E4/E3 > E3/E3 > E3/E2. It has been thought possible that the apoE gene might be involved in the modulation of dietary plasma cholesterol responses, perhaps explaining the differences in cholesterol concentrations. Some dietary intervention studies have suggested that apoE4 individuals react to dietary change with exaggerated cholesterol responses. In one study, apoE4/E4 individuals responded by increased cholesterol reductions during low fat intake, and by increased cholesterol elevations during switchback to high fat diet. Plausible mechanisms have been postulated which could explain such differences. However, other studies have reported no differences in plasma lipid responses among apoE phenotypes. The studies cannot be directly compared because of different designs and study populations with differing apoE allele frequencies. Thus the possible role of genetic variation in the apoE gene in the modulation of dietary plasma lipid responses remains to be confirmed in prospective dietary studies, involving diets both rich and poor in fat and cholesterol.