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

• Published in: Annals of clinical and laboratory science Vol. 31; no. 2; pp. 163 - 170
• Main Authors: HIDAKA, Hiroya, TOZUKA, Minoru, HIDAKA, Eiko, YAMAUCHI, Kazuyoshi, OTA, Hiroyoshi, HONDA, Takayuki, KATSUYAMA, Tsutomu
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA Institute for Clinical Science 01.04.2001
• Subjects: Adult; Apolipoproteins E - blood; Apolipoproteins E - chemistry; Apolipoproteins E - genetics; Biological and medical sciences; Chromatography, Affinity; Electrophoresis, Agar Gel; Electrophoresis, Gel, Two-Dimensional; Electrophoresis, Polyacrylamide Gel; Errors of metabolism; Female; Genetic Variation; Humans; Hypertriglyceridemia - genetics; Isoelectric Focusing; Isoelectric Point; Lipids (lysosomal enzyme disorders, storage diseases); Male; Medical sciences; Metabolic diseases; Phenotype; Receptors, LDL - metabolism; Human; Evaluation; Family study; Genetic variant; Etiopathogenesis; Metabolic diseases; Lipids; Hyperlipoproteinemia; Enzymopathy; Genetic determinism; Case study; Binding protein; Apolipoprotein E; Hypertriglyceridemia; Isoelectric point; Adult; Female; Dyslipemia
• ISSN: 0091-7370; 1550-8080

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 indicated that 3 possess the same variant. All 4 had a high concentration of apoE in plasma, while 3 of 4 had hypertriglyceridemia. In the proband (who had no hypertriglyceridemia), most apoE was distributed in slow-alpha lipoproteins (predominantly in the form of apoE-AII heterodimer) and in larger molecules 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. In each subject, the concentration of apoE3 variant was significantly higher than that of normal apoE3 in the predominant apoE-rich lipoprotein. The apoE3 variant, which displayed a slightly reduced binding ability to LDL-receptor and heparin, may induce an accumulation of apoE-rich lipoproteins. These observations suggest that the difference in distribution of apoE3 variant in plasma lipoproteins between the proband and her brother (combined with its reduced affinity for the LDL receptor) may provide key insights into the pathogenesis of hypertriglyceridemia.