Cholesteryl ester transfer protein and high density lipoprotein responses to cholesterol feeding in men: relationship to apolipoprotein E genotype.
The apolipoprotein (apo) E isoform is an important determinant of the plasma lipoprotein distribution of apoE and of the metabolism of apoE-containing lipoproteins. We have determined the effects of apoE genotype on the plasma lipoprotein response to cholesterol feeding in 30 young normal male subjects (5 E3/2, 11 E3/3, 14 E4/3) under rigorously controlled dietary conditions. Two diets, differing only in cholesterol content (low cholesterol (LC): 80 mg cholesterol/1000 kcal and high cholesterol (HC): 320 mg cholesterol/1000 kcal), were compared using a random crossover design. At the end of the HC as compared to the LC period, total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), and HDL2-C increased by an average of 15%, 21%, 7%, and 23%, respectively, for the three genotype groups combined (P < 0.001 for each). The LDL-C response to dietary cholesterol did not differ among the apoE genotypes. However, the increase in HDL-C varied significantly according to the apoE genotype (E3/2: 0 change, E3/3: +4%, E4/3: +12%; P < 0.05). The plasma cholesteryl ester transfer protein (CETP) response to cholesterol feeding also differed amongst the three apoE genotype groups (E3/2: +37%, E3/3: +18%, E4/3: +9%) (P < 0.05). ApoE genotype has significant and opposite effects on plasma CETP and HDL-C responses to dietary cholesterol in men.
Martin
L J
LJ
Lipoprotein and Atherosclerosis Group, McGill University, Canada.
Connelly
P W
PW
Nancoo
D
D
Wood
N
N
Zhang
Z J
ZJ
Maguire
G
G
Quinet
E
E
Tall
A R
AR
Marcel
Y L
YL
McPherson
R
R
D000273:Adipose Tissue / Q000378:metabolism; D001057:Apolipoproteins E / Q000235:genetics*; D002352:Carrier Proteins / Q000097:blood* / Q000235:genetics; D002784:Cholesterol / Q000097:blood; D053480:Cholesterol Ester Transfer Proteins; D002791:Cholesterol, Dietary / Q000008:administration & dosage / Q000494:pharmacology*; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D005838:Genotype; D006023:Glycoproteins; D006801:Humans; D008075:Lipoproteins, HDL / Q000097:blood*; D008297:Male; D012333:RNA, Messenger / Q000378:metabolism
D001057:Apolipoproteins E; C506642:CETP protein, human; D002352:Carrier Proteins; D053480:Cholesterol Ester Transfer Proteins; D002791:Cholesterol, Dietary; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D006023:Glycoproteins; D008075:Lipoproteins, HDL; D012333:RNA, Messenger; D002784:Cholesterol