FAMILIAL HYPOBETALIPOPROTEINEMIA IS NOT ASSOCIATED WITH LOW-LEVELS OFLIPOPROTEIN(A)

To assess whether very low concentrations of LDL affected lipoprotein( a) [Lp(a)] concentrations and apo(a) associations with lipoproteins, w e studied Lp(a) levels and associations in heterozygous subjects with familial hypobeta-lipoproteinemia FHBL) associated with several trunca ted forms of apoB-100, ranging from apoB-31 to apoB-89. Distributions of apo(a) isotypes were assessed by a combined electrophoresis-immunob lotting procedure that detects 34 isoforms. Lp(a) concentrations were quantified by two ELISAs, one detecting total apo(a) and the other apo B-bound apo(a) in plasma. Associations of apo(a) with plasma lipoprote ins were evaluated by gel permeation chromatography (FPLC) and DGUC fo llowed by analyses of elution and gradient fractions by apo(a) ELISA. In addition, associations were examined by nondenaturing electrophores is or immunoprecipitation of whole plasma and examination of contents by immunoblotting. Finally, interactions between r-apo(a) and LDLs wer e evaluated in reconstitution experiments. The distributions of apo(a) isotypes did not differ between FHBL-affected and unaffected members of the same kindreds, and concentrations of Lp(a) were similar even wh en subjects were matched for isotypes both within and across kindreds. In subjects heterozygous for apo(a) isoforms, the smaller isoforms we re inversely related to Lp(a) concentrations, the larger isoforms were not. The regression lines between Lp(a) concentrations and the smalle r apo(a) isoforms were significant and negative in slope for both FHBL -affected and unaffected subjects, but the slopes of the lines did not differ. In multiple regression analyses, only the sizes of the smalle r apo(a) isoforms contributed to the prediction of Lp(a) concentration s. ApoB-size made no difference. In simple apoB-100/apoB-truncation he terozygotes, virtually all apo(a) was complexed with apoB-100-containi ng particles but not apoB-truncation particles, and r-apo(a) recombine d with apoB-100-containing LDLs but not with apoB-89-containing LDLs. Thus, (1) low apoB levels do not affect the plasma concentrations of L p(a), (2) apo(a) binds apoB-100 to form Lp(a) particles of usual sizes and densities, and (3) apoB truncations even as large as apoB-89 do n ot form covalent bands with apo(a), although noncovalent associations with apoB-89 may be present in plasma.