Am. Dart et B. Cooper, Independent effects of Apo E phenotype and plasma triglyceride on lipoprotein particle sizes in the pasting and postprandial states, ART THROM V, 19(10), 1999, pp. 2465-2473
LDL particle sizes and Apo E phenotypes were determined in 212 subjects of
whom 51 had angina. LDL diameter was significantly less in subjects with an
epsilon 2 allele (24.76 +/- 0.08 vs 24.94 +/- 0.02 nm, P=0.02), and this w
as evident for both E2/E3 (24.77 +/- 0.09 nm) and E2/E4 (24.69 +/- 0.08 nm)
phenotypes. Although there was a negative relation between LDL diameter an
d plasma triglyceride, the effect of apo E2 was still evident with adjustme
nt for triglyceride. In multiple regression analysis, the significant deter
minants of LDL diameter were gender (with females having larger particles t
han males), body mass index, and the presence (or absence) of E2. HDL parti
cle sizes and compositions were determined on fasting samples and, addition
ally, 5 and 8 hours after a fat-rich meal for 48 coronary heart disease cas
es and 49 control subjects. Fasting HDL particle sizes were not related to
the presence of E2 but were significantly smaller for subjects possessing a
n epsilon 4 allele (8.09+/-0.08 vs 8.39+/-0.05 nm, P=0.003) and were negati
vely related to plasma triglyceride. However, the effect of E4 persisted af
ter adjustment for triglyceride. In a multiple regression analysis, the onl
y significant determinant of fasting HDL diameter was the presence (or abse
nce) of E4 with fasting plasma triglyceride just failing to reach significa
nce (P=0.06); There was a postprandial increase in HDL diameter that was le
ss marked in subjects with coronary heart disease. The postprandial increas
e in HDL diameter was of sufficient magnitude to result in size reclassific
ation of HDL particles. The influence of E4 was also evident at both postpr
andial time points. Compositional analysis demonstrated that the increase i
n HDL diameters postprandially could be attributed to triglyceride enrichme
nt, with an accompanying fall in cholesterol ester content. Phospholipid ch
anges postprandially were biphasic with an initial fall followed by a rise
in concentration. The increase in triglyceride content was significantly le
ss in those subjects with angina despite an equivalent rise in plasma trigl
yceride. The present study demonstrates significant, but different, effects
of variation in apo E phenotype on the particle sizes of both HDL and LDL.
Such effects were still evident with adjustment for differences in plasma
triglyceride and suggests that variation in apo E phenotype exerts effects
on lipoprotein particle sizes by mechanisms additional to those dependent o
n change in plasma triglyceride.