LDL composition in E2/2 subjects and LDL distribution by Apo E genotype in type 1 diabetes.
Apo E plays an important role in chylomicron and VLDL remnant processing, uptake or conversion to LDL. The type of lipoprotein that isolates in the LDL density of E2/2 subjects was investigated and the effect of the apo E isoforms on LDL mass was determined in all genotypes in a large group of Type 1 diabetics. Analysis of the LDL composition of E2/2 homozygotes (n=6) compared to subjects with the common E3/3 isoform (n=6) demonstrated an enrichment in apo E, unesterified cholesterol, phospholipid and triglyceride relative to apo B in E2/2 subjects, more typical of a dense IDL remnant than of LDL. Although diabetics were studied, these findings are considered to reflect those of the general population. Comparison of the lipoprotein distribution of homozygous and heterozygous subjects revealed that, as genotype changed from E4/4 (n=22) to E3/4 (n=262), E3/3 (n=710)=E2/4 (n=30), E2/3 (n=151), E2/2 (n=6), LDL cholesterol decreased significantly in a stepwise manner. The decrease was not in a specific subgroup of LDL. In conclusion, for E2/2 subjects, lipoproteins isolated in the LDL density range appear to be composed mainly of dense IDL remnants and some Lp(a). The apo E isoform also has a significant effect on LDL concentration in both homozygotes and heterozygotes.
Murdoch
Susan J
SJ
Division of Metabolism, Endocrinology and Nutrition, Department of Medicine, University of Washington, Seattle, WA 98195, United States. smurdoch@u.washington.edu <smurdoch@u.washington.edu>
Boright
Andrew P
AP
Paterson
Andrew D
AD
Zinman
Bernard
B
Steffes
Michael
M
Cleary
Patricia
P
Edwards
Karen
K
Marcovina
Santica S
SS
Purnell
Jonathan Q
JQ
Brunzell
John D
JD
D000328:Adult; D053329:Apolipoprotein E2 / Q000235:genetics*; D053318:Apolipoprotein E3 / Q000235:genetics; D002784:Cholesterol / Q000097:blood* / Q000378:metabolism; D008078:Cholesterol, LDL / Q000097:blood* / Q000378:metabolism*; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000235:genetics* / Q000378:metabolism*; D005260:Female; D005838:Genotype; D006801:Humans; D006949:Hyperlipidemias / Q000235:genetics; D008074:Lipoproteins / Q000097:blood* / Q000378:metabolism; D008297:Male; D008875:Middle Aged
D053329:Apolipoprotein E2; D053318:Apolipoprotein E3; D008078:Cholesterol, LDL; D008074:Lipoproteins; C030104:lipoprotein cholesterol; D002784:Cholesterol