PATHOLOGY OF THE HUMAN APOLIPOPROTEIN-E G ENE

Apolipoprotein E (apo E) is a polymorphic glycoprotein that plays an e ssential part in the binding to receptors for the uptake of chylomicro ns and VLDL remnants and of LDL. The three major isoforms are E3 (Cys1 12/Arg158), E4 (Arg112/Arg158) and E2 (Cys112/Cys158). The apo E genet ic variation has a great impact. In most of type III familial hyperlip oproteinemias (HLP), E2 is implicated at the homozygote status. In oth er cases, rare alleles are directly responsible for dominant type III HLP. Apo E polymorphism is an essential determinant in the interindivi dual variations of lipids in healthy subjects in various populations. Its influence can be significant on the efficacy of nutritional or the rapeutic interventions. The allele epsilon4 appears to be associated w ith an increased risk of premature atherosclerosis. Recently, epsilon4 was demonstrated to be associated with an early Alzheimer's disease o nset. Apo E polymorphism contributes to the lipid disorders in diabete s and obesity. The analysis of apo E polymorphism can be carried out w ith two conceptually different approaches. The first one is based on t he separation of plasma isoforms of the protein by isoelectric focusin g or bidimensional electrophoresis. The other one consists in the appl ication of molecular biology techniques (PCR and endonuclease restrict ion profiles) for a detection of the common alleles and of several rar e alleles, avoiding the possible errors of the phenotyping technique o f the apo E protein. The application of genetic engineering allows a b etter understanding,of the role played by apo E towards its receptors and in other molecular interactions which are not well known up to now .