The effect of genetic determinants of low density lipoprotein levels on lipoprotein (a).
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.
Hegele
R A
RA
Howard Hughes Medical Institute, University of Utah Medical Centre, Salt Lake City.
Sutherland
S
S
Robertson
M
M
Wu
L
L
Emi
M
M
Hopkins
P N
PN
Williams
R R
RR
Lalouel
J M
JM
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
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