Differential distribution of apolipoprotein E isoforms in human plasma lipoproteins.
The polymorphism of apolipoprotein E (apo E) accounts for a substantial amount of the genetic variance of cholesterol levels in man. The epsilon-2 allele and the epsilon-4 allele raises plasma and low density lipoprotein cholesterol levels as compared to the epsilon-3 allele. Whereas the lower cholesterol levels in carriers of the epsilon-2 allele can, at least in part, be attributed to the grossly deficient binding of apo E-2 to the apo B,E receptor, apo E-3 and E-4 bind to the same degree. We used gel filtration and ultracentrifugation to separate lipoproteins and subsequent immunoblotting analysis to study the apo E isoform distribution. We always found lipoproteins of lower density relatively enriched in apo E-4 and high density lipoproteins relatively depleted of apo E-4 as compared to apo E-3. This was also seen in plasma of heterozygous subjects that simultaneously express two apo E isoforms. Also, the apo E-A-II complex was directly shown by immunoblotting. Furthermore, when purified iodinated apo E was incubated with plasma in vitro, apo E-4 also reassociated more with lipoproteins of lower density than apo E-3. We conclude that apo E-3 and apo E-4 have a different lipoprotein particle distribution in vivo. This differential lipoprotein distribution may account for differences in the metabolism between apo E-3 and E-4.
Steinmetz
A
A
Zentrum Innere Medizin, Endokrinologie und Stoffwechsel, Philipps-Universität, Marburg, West Germany.
Jakobs
C
C
Motzny
S
S
Kaffarnik
H
H
D053329:Apolipoprotein E2; D053318:Apolipoprotein E3; D053327:Apolipoprotein E4; D001057:Apolipoproteins E / Q000032:analysis* / Q000235:genetics; D002850:Chromatography, Gel; D004591:Electrophoresis, Polyacrylamide Gel; D006579:Heterozygote; D006801:Humans; D015151:Immunoblotting; D008074:Lipoproteins / Q000032:analysis* / Q000097:blood
D053329:Apolipoprotein E2; D053318:Apolipoprotein E3; D053327:Apolipoprotein E4; D001057:Apolipoproteins E; D008074:Lipoproteins