Hypobetalipoproteinemia in many kindreds is associated with truncated forms of
apoB-100. Mutations of the
apoB gene specifying more than 20 different carboxyl terminal truncations of
apoB have been identified ranging in length from apoB-2 to
apoB-89. Truncations longer than
apoB-48 appear to be secreted only by liver, while truncations shorter than
apoB-48 are secreted by liver as well as intestine. Thus, intestines of subjects heterozygous for truncations >
apoB-48 contain two alleles producing
apoB-48, while intestines of heterozygotes with truncations <
apoB-48 contain only one allele producing
apoB-48. Our aims were to assess whether intestinal fat absorption differed from normal in subjects with
apoB-truncation-associated
hypobetalipoproteinemia and whether fat absorption in heterozygotes with
apoB < 48 differed from heterozygotes with
apoB > 48. Ten subjects heterozygous for
apoB > 48 (apoBs -89, -75, -54, -52), six heterozygous for
apoB < 48 (apoBs -46, -40, -31) and a group of 16 controls matched for age, sex, body mass index characteristics, and eating similar diets were given identical fat meals containing
vitamin A. Plasma
triglycerides in whole plasma and
retinyl palmitate in
chylomicron and non-
chylomicron (remnant) fractions were analyzed at zero time and over the next 14 hours. Fasting
vitamins A and E also were quantified. Fasting plasma levels of
vitamin E were lower in heterozygotes (536 +/- 198 mg/l for
apoB > 48 vs. 372 +/- 155 for
apoB < 48) versus controls (1162 +/- 441), but were not different when corrected for differences in
LDL-C. Plasma
vitamin A levels (uncorrected) were not different. Meal responses were characterized in terms of peak concentrations and areas under the curves (after subtraction of minimum points). These indices of fat absorption were comparable in all
apoB phenotype groups suggesting that one allele specifying the intestinal production of
apoB-48 is sufficient for normal fat absorption.