title: Apolipoprotein A-I metabolism in subjects with a PstI restriction fragment length polymorphism of the apoA-I gene and familial hypoalphalipoproteinemia.
abstract: Familial hypoalphalipoproteinemia (hypoalpha), characterized by a decreased high density lipoprotein level, is associated with an increased incidence of premature cardiovascular disease. Restriction fragment length polymorphism analysis of genomic DNA has detected a polymorphism for the PstI restriction endonuclease near the apoA-I gene, with either a 2.2 or a 3.3 kb fragment. The latter has been previously found to occur with significantly higher frequency in probands of families with familial hypoalpha. ApoA-I was isolated from three unrelated subjects with familial hypoalpha and the 3.3 kb PstI polymorphism of the apoA-I gene, and from normal control subjects. The apoA-I from the hypoalpha subjects was structurally normal as determined by amino acid analysis and by two-dimensional gel electrophoresis. When normal apoA-I and hypoalpha apoA-I were simultaneously injected into either normal controls or hypoalpha subjects, both forms of apoA-I were catabolized at the same rate in the same subject, indicating that the hypoalpha apoA-I is also metabolically normal. Analysis of the kinetics of metabolism of apoA-I in the hypoalpha subjects, compared to the normal controls, revealed that the reduced plasma levels of apoA-I were due to an increased apoA-I fractional catabolic rate, and that the synthetic rate was normal. Based on these results, we conclude that the apoA-I gene in these hypoalpha subjects is normal, and the PstI polymorphism near the apoA-I gene, which is associated with familial hypoalpha, is likely to be a marker for a mutant gene closely linked to, but not in, the apoA-I gene.
authors.affiliation: Molecular Disease Branch, National Institutes of Health, Bethesda, MD.
authors.forename: P
authors.initials: P
authors.lastname: Roma
authors.forename: R E
authors.initials: RE
authors.lastname: Gregg
authors.forename: C
authors.initials: C
authors.lastname: Bishop
authors.forename: R
authors.initials: R
authors.lastname: Ronan
authors.forename: L A
authors.initials: LA
authors.lastname: Zech
authors.forename: M V
authors.initials: MV
authors.lastname: Meng
authors.forename: C
authors.initials: C
authors.lastname: Glueck
authors.forename: C
authors.initials: C
authors.lastname: Vergani
authors.forename: G
authors.initials: G
authors.lastname: Giudici
authors.forename: H B
authors.initials: HB
authors.lastname: Brewer
mesh_terms: D000328:Adult; D000596:Amino Acids / Q000032:analysis; D016632:Apolipoprotein A-I; D001054:Apolipoproteins A / Q000235:genetics* / Q000378:metabolism; D015252:Deoxyribonucleases, Type II Site-Specific / Q000378:metabolism; D015180:Electrophoresis, Gel, Two-Dimensional; D005796:Genes; D006801:Humans; D007525:Isoelectric Focusing; D007700:Kinetics; D008075:Lipoproteins, HDL / Q000235:genetics* / Q000378:metabolism; D008297:Male; D012150:Polymorphism, Restriction Fragment Length; D013631:Tangier Disease / Q000235:genetics* / Q000378:metabolism
chemical_list: D000596:Amino Acids; D016632:Apolipoprotein A-I; D001054:Apolipoproteins A; D008075:Lipoproteins, HDL; C024388:CTGCAG-specific type II deoxyribonucleases; D015252:Deoxyribonucleases, Type II Site-Specific