[Apolipoprotein E and its alleles in healthy subjects and in atherosclerosis].
Apolipoprotein E (apo E) plays a central role in lipoprotein metabolism as a ligand for LDL-, VLDL- and remnant receptors. It is mainly synthesized by hepatocytes and also by monocytes-macrophages. There are three common codominant isoforms E2, E3 and E4. Apo E2 binds defectively to LDL- and to remnant-receptors. Apo E alleles frequency varies from population to population around the world. In Europe, E4 allele frequency increases from south to north along the cardiovascular disease frequency gradient. On the other hand, the association between E2 allele and these diseases remains to be proved except for type III hyperlipoproteinemia. Apo E4 role in atherosclerosis could be explained, at least in part, by its high solubility in apo B lipoproteins. The average cholesterolemia of E4/E3 subjects is higher than E3/E3 subjects and E3/E3 subjects' cholesterolemia is higher than in E3/E2 subjects, probably because of a faster uptake of chylomicrons and VLDL remnants in E4/E3 subjects. The E4 allele also seems to play a role not only in diet response in combination with other genetic factors such as the Eco RI polymorphism of apo B but also in hypolipemic treatment. Apo E plays also a role in triglyceridemia control in association with other genetic and environmental factors such as lipoprotein lipase, apo B, LDL receptor and diet. Models of apo E knockout mice suggest a protective effect of monocyte-macrophageapo E in the vessel wall and HDL-apo E probably induces a high cholesterol efflux from macrophages. This effect counteracts the proatherogenic effect of VLDL- and IDL-apo E. The balance between these effects could be influenced by apo E phenotype.
Couderc
R
R
Service de biochimie, Hôpital Tenon, Paris.
Bailleul
S
S
D000483:Alleles; D000818:Animals; D001057:Apolipoproteins E / Q000235:genetics* / Q000378:metabolism; D001161:Arteriosclerosis / Q000235:genetics* / Q000378:metabolism; D002318:Cardiovascular Diseases / Q000209:etiology / Q000235:genetics; D005787:Gene Frequency; D006801:Humans; D006952:Hyperlipoproteinemia Type III / Q000235:genetics; D008024:Ligands; D008099:Liver / Q000378:metabolism; D012307:Risk Factors
D001057:Apolipoproteins E; D008024:Ligands
L'apolipoprotéine E et ses allèles chez le sujet sain et au cours de l'athérosclérose.