Apolipoprotein E polymorphism and coronary heart disease.

Serum lipoproteins and apolipoproteins were analyzed in 199 patients with acute myocardial infarction (CCU group), and in 211 normal healthy individuals (control group). It was shown that serum lipoprotein abnormalities, especially elevated low density lipoprotein (LDL) levels, are closely related to atherogenesis in relatively young patients and in subjects with severe coronary lesions. The frequency of apo E4 was higher and that of E2 was lower in the CCU group than in the control group. Apo E mutants, E7 and E5, were also frequent in the CCU group. Subjects with an E3/2 phenotype had reduced LDL and increased VLDL levels, and those with an E4/3 phenotype had increased LDL levels in serum. These results suggest that apo E4 is a positive risk factor and apo E2 a negative risk factor for atherosclerosis. The action of apo E isoproteins to increase or decrease serum LDL levels may be one of the mechanisms of atherosclerosis. Furthermore, the effect of apo E isoforms on serum lipoproteins was evident even in childhood. The mutant apo E binding to LDL receptors were investigated to clarify the metabolism of apo E5 and apo E7. The affinity of apo E5 was twice that of the wild form of apo E3. Apo E7, however, had a lower receptor affinity than apo E3. Therefore, the authors postulate that individuals with apo E5 have increased risk of developing hypercholesterolemia and subsequent atherosclerosis. From the binding data of apo E7, the action of apo E7 is considered similar to that of apo E2.