Summary
Apolipoprotein E phenotypes were determined in 361 patients with hyperlipidemia and in controls. The E2 isoform was significantly more frequent in the group of hyperlipidemics (P<0.0005). This was not due to a higher frequency of E-2/2 homozygotes with type III hyperlipoproteinemia, but rather to a significantly higher frequency of E2 heterozygotes (P<0.0005). Subgrouping of hyperlipidemics into patients with a) hypertriglyceridemia, b) hypercholesterolemia and c) mixed hyperlipidemia revealed i) that isoform E2 was significantly more frequent in patients with hypertriglyceridemia (0.001>P>0.005), ii) that isoform E4 was significantly more frequent in patients with hypercholesterolemia (0.01>P>0.005) and iii) that isoforms E2 (P>0.005) and E4 (0.05>P>0.025) were both more frequent in patients with mixed hyperlipidemia. Roughly 20% of patients with mixed hyperlipidemia had one of the rare phenotypes E-4/4,-4/2 or-2/2. We conclude that alleles ε2 and ε4 both contribute to the susceptibility for, and/or phenotypic expression of hyperlipidemia. Whereas the gene ε2 seems to exert its influence on plasma lipoproteins by an abnormal gene product (E2) that has reduced binding activity to lipoprotein receptors, the mechanism underlying the association of the ε4 gene with hyperlipidemia is presently unclear.
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Utermann, G., Kindermann, I., Kaffarnik, H. et al. Apolipoprotein E phenotypes and hyperlipidemia. Hum Genet 65, 232–236 (1984). https://doi.org/10.1007/BF00286508
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DOI: https://doi.org/10.1007/BF00286508