APO-E VARIANTS IN PATIENTS WITH TYPE-III HYPERLIPOPROTEINEMIA

Type III hyperlipoproteinemia (HLP III) is characterized by the reduce d catabolism and accumulation of chylomicron and very low density lipo protein (VLDL) remnants. Most HLP III patients are homozygous for the apolipoprotein E2 (Cys(112), Cys(158)) allele; however, several other mutations at this gene locus have been associated with this HLP. In or der to assess the presence of rare apo E variants in our population, w e have examined apo E phenotypes by isoelectric focusing (IEF) and gen otypes by restriction enzyme analysis of polymerase chain reaction (PC R) amplified DNA in 15 patients with HLP III. Lack of concordance betw een these two methods was observed in 11 subjects (73.3%). DNA sequenc ing analysis of the receptor binding domain of the apo E gene in the 1 1 HLP III patients with discrepancies demonstrated the presence of six carriers of the epsilon 3 (Arg(136) --> Ser) allele and three carrier s of the epsilon 2 (Gly(127) --> Asp) allele. Five HLP III patients we re apo E2/E2 using IEF, but only 2 of them were epsilon 2 homozygous u sing PCR. Two patients were E3/E3 homozygous with normal DNA sequence in the low density lipoprotein receptor binding domain of apo E. In co nclusion, our results show that a number of different apo E genotypes are associated with HLP III in this population. More specifically, mut ations at positions 127 and 136 might be frequent in Spain and occur i n patients with HLP III.