title: Comparison of apolipoprotein B metabolism in familial defective apolipoprotein B and heterogeneous familial hypercholesterolemia.
abstract: Both defective LDL receptors (familial hypercholesterolaemia, FH) and mutations in apolipoprotein B (apoB) on LDL (familial defective apoB, FDB) give rise to a phenotype of elevated LDL cholesterol. We sought to compare the metabolic basis of the two conditions by examining apoB turnover in FDB and FH subjects. A group comprising three heterozygous and one homozygous FDB subjects were compared with five FH heterozygotes and 17 control subjects using a deuterated leucine tracer. Kinetic parameters were derived by multicompartmental modelling. FH heterozygotes had a reduced delipidation rate for VLDL, which led to a moderate increase in plasma triglyceride. Compared with controls and FH, the FDB subjects converted 44% less IDL to LDL. The LDL FCR was reduced to a similar extent in FDB and FH. In all subjects LDL plasma levels appeared to be regulated by the LDL FCR and the rate of production of small VLDL. We conclude that disturbances in IDL metabolism provide the basis for understanding why FDB is less severe than FH. Our findings suggest that an apoB-LDL receptor interaction is important in the IDL to LDL conversion.
authors.affiliation: Department of Pathological Biochemistry, Glasgow Royal Infirmary, North Glasgow Hospitals University NHS trust, 4th floor, Queen Elizabeth Building, Alexandra Parade, Glasgow G31 2ER, Scotland, UK. dairena.gaffney@clinmed.gla.ac.uk
authors.forename: Dairena
authors.initials: D
authors.lastname: Gaffney
authors.forename: Lorne
authors.initials: L
authors.lastname: Forster
authors.forename: Muriel J
authors.initials: MJ
authors.lastname: Caslake
authors.forename: Dorothy
authors.initials: D
authors.lastname: Bedford
authors.forename: J Philip
authors.initials: JP
authors.lastname: Stewart
authors.forename: Grace
authors.initials: G
authors.lastname: Stewart
authors.forename: Gilbert
authors.initials: G
authors.lastname: Wieringa
authors.forename: Marek
authors.initials: M
authors.lastname: Dominiczak
authors.forename: J Paul
authors.initials: JP
authors.lastname: Miller
authors.forename: Chris J
authors.initials: CJ
authors.lastname: Packard
mesh_terms: D000012:Abetalipoproteinemia / Q000150:complications / Q000235:genetics* / Q000378:metabolism*; D000328:Adult; D001055:Apolipoproteins B / Q000235:genetics* / Q000378:metabolism*; D002784:Cholesterol / Q000097:blood; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D015243:Cholesterol, VLDL / Q000097:blood; D005192:Family Health; D018740:Genetic Heterogeneity; D005819:Genetic Markers / Q000235:genetics; D006720:Homozygote; D006801:Humans; D006938:Hyperlipoproteinemia Type II / Q000150:complications / Q000235:genetics* / Q000378:metabolism*; D008074:Lipoproteins / Q000097:blood; D008875:Middle Aged; D011973:Receptors, LDL / Q000097:blood / Q000235:genetics; D012606:Scotland; D014280:Triglycerides / Q000097:blood
chemical_list: D001055:Apolipoproteins B; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D015243:Cholesterol, VLDL; D005819:Genetic Markers; D008074:Lipoproteins; D011973:Receptors, LDL; D014280:Triglycerides; C030104:lipoprotein cholesterol; D002784:Cholesterol