Familial defective apolipoprotein (apo) B-100 (FDB) is a frequent cause of
hypercholesterolemia. Hypercholesterolemia in homozygous FDB is less severe
than in homozygotes for familial hypercholesterolemia. Recently, we showed
decreased low density lipoprotein (LDL) apoB-100 fractional catabolism and
decreased production of LDL due to an enhanced removal of apoE-containing
precursors in a patient with homozygous FDB. The effects of defective apoB-
100 on high density lipoprotein (HDL) metabolism are unknown. We studied HD
L apoA-I metabolism in this FDB patient and in 6 control subjects by using
H-2(3)-L-leucine as a tracer. ApoA-I levels were normal in all study subjec
ts. However, the fractional catabolic rate and the production rate of apoA-
I were increased, by 79% and 70%, respectively, in FDB; the fractional cata
bolic rate of apoA-I in FDB was 0.34 day(-1) compared with 0.19 +/- 0.03 da
y(-1) in normal controls. The production rate of apoA-I in FDB was 18.4 mg(
.)kg(-1.)d(-1) compared with 10.8 +/- 2.3 mg(.)kg(-1.)d(-1) in controls. Th
us, we have shown for the first time that defective apoB-100 may influence
HDL kinetics, The increase in total HDL turnover might enhance reverse chol
esterol transport and could contribute to the seemingly benign clinical cou
rse of FDB compared with that of familial hypercholesterolemia.