title: The effect of genetic determinants of low density lipoprotein levels on lipoprotein (a).
abstract: Levels of Lipoprotein(a) [Lp(a)] correlate directly with atherosclerosis risk. The Lp(a) particle is physically and chemically similar to low density lipoprotein (LDL), the main difference being the presence of apolipoprotein(a) [apo(a)] bonded to the apoB-100 moiety of LDL. Genetic variation of apo(a) primarily determines Lp(a) phenotype. However, other genetic factors may also have a role in determining Lp(a) levels. Large families provide a unique opportunity to evaluate the contribution of genetic factors to disease. In several large Utah kindreds with various genetic abnormalities of lipoprotein metabolism we determined that: 1) Lp(a) levels are associated with defects at the apoB gene; 2) Lp(a) levels are not associated with defects at the LDL-receptor gene; 3) high density lipoprotein (HDL) levels are associated with genetic variation at the apo(a) locus; and 4) the DNA sequence of the apoB-100 binding domain does not vary between siblings with high and low Lp(a) levels.
authors.affiliation: Howard Hughes Medical Institute, University of Utah Medical Centre, Salt Lake City.
authors.forename: R A
authors.initials: RA
authors.lastname: Hegele
authors.forename: S
authors.initials: S
authors.lastname: Sutherland
authors.forename: M
authors.initials: M
authors.lastname: Robertson
authors.forename: L
authors.initials: L
authors.lastname: Wu
authors.forename: M
authors.initials: M
authors.lastname: Emi
authors.forename: P N
authors.initials: PN
authors.lastname: Hopkins
authors.forename: R R
authors.initials: RR
authors.lastname: Williams
authors.forename: J M
authors.initials: JM
authors.lastname: Lalouel
mesh_terms: D053299:Apolipoprotein B-100; D001054:Apolipoproteins A / Q000235:genetics; D001055:Apolipoproteins B / Q000235:genetics; D001483:Base Sequence; D001665:Binding Sites; D008076:Cholesterol, HDL / Q000097:blood; D004247:DNA / Q000235:genetics; D014644:Genetic Variation; D006801:Humans; D006938:Hyperlipoproteinemia Type II / Q000097:blood / Q000235:genetics*; D006995:Hypobetalipoproteinemias / Q000097:blood / Q000235:genetics*; D017270:Lipoprotein(a); D008074:Lipoproteins / Q000097:blood* / Q000235:genetics; D008075:Lipoproteins, HDL / Q000097:blood; D008969:Molecular Sequence Data; D011973:Receptors, LDL / Q000235:genetics
chemical_list: D053299:Apolipoprotein B-100; D001054:Apolipoproteins A; D001055:Apolipoproteins B; D008076:Cholesterol, HDL; D017270:Lipoprotein(a); D008074:Lipoproteins; D008075:Lipoproteins, HDL; D011973:Receptors, LDL; D004247:DNA