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(Arteriosclerosis, Thrombosis, and Vascular Biology. 1997;17:873-880.)
© 1997 American Heart Association, Inc.

Articles

Subjects With ApoA-I(Lys₁₀₇0) Exhibit Enhanced Fractional Catabolic Rate of ApoA-I in Lp(AI) and ApoA-II in Lp(AI With AII)

Marju Tilly-Kiesi; Alice H. Lichtenstein; Jose M. Ordovas; Gregory Dolnikowski; Raija Malmström; Marja-Riitta Taskinen; ; Ernst J. Schaefer

From the Lipid Metabolism Laboratory and Mass Spectrometry Laboratory, Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, Boston, Mass, and Helsinki University Central Hospital, Finland (M.T.-K., R.M., M.-R.T.).

Correspondence to Dr Marju Tilly-Kiesi, MD, PhD, Department of Medicine, Helsinki University Central Hospital, Haartmaninkatu 4, FIN-02900 Helsinki, Finland.

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 Lys₁₀₇ in the mature apoA-I. Patients with this mutation [apoA-I(Lys₁₀₇0)] 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 [5,5,5-²H₃]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(Lys₁₀₇0) 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(Lys₁₀₇0) 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.

Key Words: apoA-I(Lys₁₀₇0) variant • Lp(AI with AII) • kinetics • metabolism • coronary heart disease • HDL cholesterol • Lp(AI)

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