A new isoform of apolipoprotein E — Apo E-5 — Associated with hyperlipidemia and atherosclerosis

Yamamura, Taku; Yamamoto, Akira; Hiramori, Katsuhiko; Nambu, Seiki

doi:10.1016/0021-9150(84)90019-4

Cited by 65 publications

(14 citation statements)

References 27 publications

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“…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).…”

Section: Discussionmentioning

confidence: 58%

“…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.…”

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confidence: 99%

“…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).…”

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Frequencies of apolipoproteins E5 and E7 in apparently healthy Japanese

et al. 1985

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SummaryHuman apolipoprotein (apo) E plays an important role in the metabolism of cholesterol and other lipids. Apo E5 and apo E7 are genetic variants of apo E and have been detected in about 5~ of Japanese patients with hyperlipidemia and ischemic heart disease. The existence of apo E5 and apo E7, however, had not been reported in apparently healthy individuals except for a few family members of the patients with apo E5 or apo E7. It has been suggested that apo E5 and apo E7 are closely related to the development of atherosclerosis. The purpose of this study is to investigate the frequency of apo E5 and apo E7 in apparently healthy Japanese and to analyze serum lipid levels of the individuals with apo E5 or apo E7.The apo E phenotypes of 197 apparently healthy Japanese adults were determined by two-dimensional gel electrophoresis. The gene frequencies ofapo E were: ~3, 0.843; ~4, 0.112; ~2, 0.038; e5, 0.006; ~7, 0.0035. Three out of 187 subjects (1.5~) were found to have apo E5 or apo E7 in heterozygous state. Two of them were heterozygous with apo E3 (apo E3/5 and apo E3/7) and the both had normal serum lipid levels, though they were more than 50 years old. The other individual was heterozygous with apo E2 (apo E2/5) and had mild hypertriglyceridemia. As to myocardial infarction, angina pectoris and cerebral infarction, no clinically abnormal findings were detected in all the three individuals with apo E5 or apo E7.The data suggest that the frequency of the individuals with apo E5 or apo E7 is of the order of 1 X and much higher than that of the homozygotes with apo E2/2 in Japanese. The data also indicate that further genetic, epidemiologic and clinical studies are required to determine whether ~5 and ~7 act as a dominant major gene, as a recessive major gene, or as

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Section: Discussionmentioning

confidence: 58%

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Frequencies of apolipoproteins E5 and E7 in apparently healthy Japanese

et al. 1985

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“…Several Apo E variants have been reported and Comparisons of coronary score and of CAD among Apo E phenotypes in angina the mean age of the male patients with onset effort some of them are considered to be atherogenic. Yamamura et al (1984) first reported E5 which is highly associated with occurrence of ischemic heart disease or cerebral infarction. The incidence of E5 is reported to be 0.002 (Ordovas et al 1987).…”

Section: Comparisons Of Composition Of Plasma Phenotypes In Females Lmentioning

confidence: 99%

Apolipoprotein E phenotypes in patients with coronary artery disease.

Miida

1990

Tohoku J. Exp. Med.

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The relationship between apolipoprotein E (Apo E) phenotypes and progression of coronary atherosclerosis was investigated in 125 patients with coronary artery disease (CAD) proven angiographically (101 males, 24 females). To elucidate the pure effect of Apo E phenotypes on lipoproteins and coronary atherosclerosis, patients with familial hypercholesterolemia were excluded from the subjects. As a control group, 129 norml healthy volunteers (84 males, 45 females) were studied. In the CAD group, VLDL and LDL levels increased and HDL level decreased regardless of Apo E phenotypes in both sexes. The incidence of E4 was higher and that of E2 was slightly lower in the CAD group than in the control group. Two patients with E5/3 who had high LDL-cholesterol levels were found in the male CAD group. LDL-cholesterol level in E3/2 was lower than in E4/3 and E3/3 in the male CAD group. VLDL-cholesterol /triglyceride and VLDL cholesterol/ phospholipid ratios in E3/2 were significantly higher than in E4/3 and E3/3 in the male CAD group, but the difference was not so marked as found in typical type III hyperlipidemia. When the male patients with effort angina were examined, coronary score (index of the severity of CAI)) was the lowest in E3/2. In addition, the mean age at the onset of CAD was significantly higher in E3/2 than in E4/3. In conclusion, E2 acts protectively against coronary atherosclerosis, while E4 promotes it through the modulation of LDL-cholesterol level. apolipoprotein E ; hypercholesterolemia ; coronary artery disease

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“…Apo E5 [APOE,E3K] was first detected in a Japanese patient with hyperlipidemia. It migrates faster than apo E3 during sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) (Yamamura et al 1984;Tajima et al 1988;Maeda et al 1989). The receptor binding activity of apo E5 [APOE,E3K] is about twice that of apo E3 (Dong et al 1990;Wardell et al 1991 (Mailly et al 1991;Ruzicka et al 1993;Feussner et al 1996;Yamanouchi et al 1994) .…”

Section: Introductionmentioning

confidence: 99%