Subjects With ApoA-I(Lys 107 →0) Exhibit Enhanced Fractional Catabolic Rate of ApoA-I in Lp(AI) and ApoA-II in Lp(AI With AII)

Abstract

Abstract Our purpose was to examine HDL metabolism in a Finnish kindred with a 3-bp deletion in the apolipoprotein (apo) A-I gene, resulting in a deletion of Lys 107 in the mature apoA-I. Patients with this mutation [apoA-I(Lys 107 →0)] have reduced plasma HDL cholesterol and lipoprotein (AI with AII) [Lp(AI w AII)] concentrations, but not Lp(AI) levels, compared with unaffected family members. Using primed constant infusions of [5,5,5- 2 H 3 ]leucine, we determined the residence time (RT) and absolute production rate (APR) of apoA-I and apoA-II entering plasma in two subpopulations of HDL particles: [Lp(AI) and Lp(AI w AII)] in three patients heterozygous for apoA-I(Lys 107 →0) and in seven healthy control subjects. In patients, the mean RT of apoA-I in Lp(AI) (3.75±1.68 days) was less than half that observed in control subjects (8.01±2.51 days, P <.05). The mean RT of apoA-I in Lp(AI w AII) was also lower in patients than in control subjects, but differences were not statistically significant (4.72±2.42 versus 6.50±2.19 days). The mean RT of apoA-II in Lp(AI w AII) was significantly lower in patients (5.24±1.65 days) than in control subjects (9.64±3.57 days, P <.05). The APR of apoA-I into Lp(AI) was twofold higher in patients (5.9±2.1 mg·kg −1 ·d −1 ) than in control subjects (2.5±0.9, P <.05). The APRs of apoA-I and apoA-II into Lp(AI w AII) were similar in patients and control subjects. Our results are consistent with the concept that patients heterozygous for the apoA-I(Lys 107 →0) mutation have enhanced fractional catabolism of apoA-I and apoA-II in both HDL subspecies, especially in Lp(AI), and an increase in apoA-I production only into Lp(AI), which may be compensatory. Therefore, only their Lp(AI w AII) levels are decreased.