New mutants of apolipoprotein E associated with atherosclerotic diseases but not to type III hyperlipoproteinemia.

Abstract

Abstract. We analyzed the heterogeneity of apo E in very low density lipoprotein from 58 hyperlipidemic subjects with or without atherosclerosis, 69 patients with ischemic heart disease, and 100 apparently healthy individuals. Apo E gene frequencies in the group of healthy individuals were comparable with those in German and American populations. The distribution of six common apo E phenotypes in the groups of hyperlipidemia and ischemic heart disease was similar to that in the healthy group.In addition to the three major isoforms of apolipoprotein E (apo E-4, E-3, and E-2) and the new one (apo E-5) which was recently found in this laboratory, we have discovered an additional series of components, which showed themselves as at least three bands on an isoelectric focusing gel in the region of E-VII through E-V, in four patients with hyperlipidemia and atherosclerosis. The new series of apo E components, named apo E-Suita, was identical with the ordinary apo E in its interaction with heparin-Sepharose gel and with antiapo E antibody. The most basic component of apo ESuita (E-VII) was the unsialylated form and other components (E-VI and E-V), the sialylated forms. Family studies revealed that apo E-Suita was determined by inheritance of a new apo E allele located at the same locus as the hitherto known apo E components.Apo E-5 and apo E-Suita isoproteins had isoelectric points more basic than apo E-3, the parent type, by two and four units of charge, respectively. While the apo ESuita isoprotein had the same molecular weight as ordinary major apo E isoproteins, the molecular weight of the apo E-5 isoprotein was -1,500-2,000 lower than the other apo E isoproteins by sodium dodecyl sulfatepolyacrylamide gel electrophoresis. The incidence of abnormal apo E components, including apo E-5 and apo E-Suita, was high among patients with hyperlipidemia and ischemic heart disease (7:127), while we could not find such components among 100 healthy individuals. Moreover, five of seven patients with the abnormal apo E had overt atherosclerotic disease. The findings suggest that these kinds of apolipoprotein mutation are closely related to the development of atherosclerosis.

Frequencies of apolipoproteins E5 and E7 in apparently healthy Japanese

“…Apo E5 and apo E7 have been detected in about 5~ of Japanese patients with hyperlipidemia and ischemic heart disease, while they were not found among 100 healthy Japanese (Yamamura et al, 1984a;Yamamura et al, 1984b). We also found four cases with apo E5 or apo E7 (4.3%) out of 92 patients with myocardial infarction (Hamaguchi et al, in preparation).…”

“…We also found four cases with apo E5 or apo E7 (4.3%) out of 92 patients with myocardial infarction (Hamaguchi et al, in preparation). Yamamura et al (1984b) observed that five of seven patients with apo E5 or apo E7 had overt atherosclerotic disease.…”

“…The three common alleles, ~2, e3 and e4, code for three common apo E isoforms, apo E2, apo E3 and apo E4, respectively and determine six apo E phenotypes (Zannis et al, 1981 ;Zannis et al, 1982;Utermann et al, 1982). Futhermore, rare mutant genes have been described (Chiselli et al, 1982;Weisgraber et al, 1984;Gregg et al, 1983;Yamamura et al, 1984a;Yamamura et al, 1984b). Besides an association of apo E2 with type III hyperlipidemia (Havel, 1982), most of apo E isoforms encoded by these rare mutant genes have been reported to be associated with hyperlipidemia or atherosclerotic diseases or both.…”

“…Besides an association of apo E2 with type III hyperlipidemia (Havel, 1982), most of apo E isoforms encoded by these rare mutant genes have been reported to be associated with hyperlipidemia or atherosclerotic diseases or both. They include apo E Bethesda (apo El) detected in a Caucasian family and apo E5 and apo E suita (apo E7) found in Japanese families (Gregg et al, 1983;Yamamura et al, 1984a;Yamamura et al, 1984b). Apo E5 and apo E7 have been thus far detected only in Japanese patients with myocardial infarction and hyperlipidemia and in their family members (Yamamura et al, 1984b).…”

“…They include apo E Bethesda (apo El) detected in a Caucasian family and apo E5 and apo E suita (apo E7) found in Japanese families (Gregg et al, 1983;Yamamura et al, 1984a;Yamamura et al, 1984b). Apo E5 and apo E7 have been thus far detected only in Japanese patients with myocardial infarction and hyperlipidemia and in their family members (Yamamura et al, 1984b).…”