title: Subjects with ApoA-I(Lys107-->0) exhibit enhanced fractional catabolic rate of ApoA-I in Lp(AI) and ApoA-II in Lp(AI with AII).
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(Lys107-->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 [5,5,5-2H3]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(Lys107-->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 x kg(-1) x 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(Lys107-->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.
authors.affiliation: Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, Boston, Mass, USA.
authors.forename: M
authors.initials: M
authors.lastname: Tilly-Kiesi
authors.forename: A H
authors.initials: AH
authors.lastname: Lichtenstein
authors.forename: J M
authors.initials: JM
authors.lastname: Ordovas
authors.forename: G
authors.initials: G
authors.lastname: Dolnikowski
authors.forename: R
authors.initials: R
authors.lastname: Malmström
authors.forename: M R
authors.initials: MR
authors.lastname: Taskinen
authors.forename: E J
authors.initials: EJ
authors.lastname: Schaefer
mesh_terms: D000328:Adult; D016632:Apolipoprotein A-I / Q000235:genetics* / Q000378:metabolism*; D016633:Apolipoprotein A-II / Q000378:metabolism*; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D005260:Female; D017353:Gene Deletion; D006579:Heterozygote; D006801:Humans; D007700:Kinetics; D008074:Lipoproteins / Q000097:blood*; D008239:Lysine; D008297:Male; D008875:Middle Aged; D014280:Triglycerides / Q000097:blood
chemical_list: D016632:Apolipoprotein A-I; D016633:Apolipoprotein A-II; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D008074:Lipoproteins; D014280:Triglycerides; D008239:Lysine