Studies on the metabolic defect in Broad‐ß disease (hyperlipoproteinaemia type III)

Abstract

The apoprotein composition of the main lipoprotein fractions (VLDL, LDL‐1, LDL‐2 and HDL) was studied initially in 15 patients with Broad‐β disease. Analytical isoelectric focusing of urea‐soluble apo‐VLDL and apo LDL‐1 demonstrated a variant pattern of the polymorphic Apoprotein E with a deficient Apo E‐III band in all patients. The Apo E‐III deficiency pattern was seen in only six out of 304 hyperlipidaemic controls. These six Apo E‐III deficient controls had characteristic signs of Broad+ disease, and thus represented patients not previously recognized as having the disorder. The Apo E focusing patterns were constant on repeated examinations and were stable under different metabolic conditions. The data show that Apo E‐III deficiency in VLDL is a specific qualitative marker for Broad‐β disease, allowing an unequivocal diagnosis that had not been possible previously. Indirect evidence suggests that Apo E‐III deficiency is the basic lipoprotein abnormality underlying the familial dyslipoproteinaemia.

Increased frequency of the apolipoprotein E‐4 isoform in male subjects with multifactorial hypercholesterolemia

“…Thus, apoE plays a major role in the metabolism of chylomicrons, very low density lipoproteins and intermediate density lipoproteins (Sherill et al 1980, Goldstein et al 1983. Subjects with type 111 hyperlipidemia are homozygous for apoE-2 (Utermann et al 1977, Brown et al 1983. Recently, the apoE-4 isoform has been found to be more frequent among hypercholesterolemic subjects (Cumming & Robertson 1984, Utermann et al 1984a).…”

Polymorphism of apolipoprotein E

“…This cut-point clearly separated individuals with dysbetalipoproteinemia from other subjects. All probands with dysbetalipoproteinemia, whether hyperlipidemic or not, were found in the groups with E-II/E-I11 ratios >2.95 (Utermann et al 1977b(Utermann et al , c, 1978.…”

“…The three common phenotypes in this system (Apo E-N, Apo E-ND and Apo E-D) are determined by two alleles designated Apo E n and Apo E d (Utermann et al 1977~). Hyperlipidemic individuals with phenotype Apo E-D all have type 111 hyperlipoproteinemia (Utermann et al 1977b); norrnolipidemic subjects with this phenotype have a lipoprotein pattern designated primary dysbetalipoproteinemia (= normolipidemic type 111). We report here on a systematic comparative evaluation of Apo E phenotypes by the new precipitation-I.E.F.…”

“…procedure and by conventional ultracentrifugation. These studies form the basis of a study clarifying the genetics of hyperlipoproteinemia type I11 which is presented in an accompanying paper (Utermann et al 1978).…”

The Genetics of the Human APOE Polymorphism

“…2,3,4 The common variants of apoE were discovered about 40 years ago 8 and their presence was confirmed at the end of 1970s in several studies. [6][7][8][9][10][11][12] In particular, it was reported that, upon two-dimensional gel electrophoretic analysis, apoE from human very-low density lipoprotein (VLDL) of different individuals appears in either one of two complex patterns, designated as class a and b. 13 In 1981, it was demonstrated that the proteins belonging to class b (b-II, b-III, and b-IV) represent homozygosity for three identical APOE gene variants.…”