Characterization of an apolipoprotein E3 variant (Arg 145 -> His) associated with mild hypertriglyceridemia

In a proband (21-yr-old female), we previously identified an apolipoprotein (apo) E variant, apoE3 (Arg 145 --> His), with an isoelectric point midway between apoE3 and apoE2. ApoE gene analysis of 4 of the proband's kin indi cated that 3 possess the same variant. All 4 had a high concentration of ap oE in plasma, while 3 of 4 had hypertriglyceridemia. In the proband (who ha d no hypertriglyceridemia), most apoE was distributed in slow-alpha lipopro teins (predominantly in the form of apoE-AII heterodimer) and in larger mol ecules with apparent. molecular weights of 80 and 100 kDa. In the proband's brother (with hypertriglyceridemia), however, most apoE was distributed in slow pre-beta lipoproteins, predominantly in the form of monomeric apoE. I n each subject, the concentration of apoE3 variant was significantly higher than that of normal apoE3 in the predominant apoE-rich lipoprotein. The ap oE3 variant, which displayed a slightly reduced binding ability to LDL-rece ptor and heparin, may induce an accumulation of apoE-rich lipoproteins. The se observations suggest that the difference in distribution of apoE3 varian t in plasma lipoproteins between the proband and her brother (combined with its reduced affinity for the LDL receptor) may provide key insights into t he pathogenesis of hypertriglyceridemia. (received 28 January 2001, accepte d February 2001).