Association between apolipoprotein E phenotype and endogenous cholesterol synthesis as measured by deuterium uptake.
OBJECTIVE
The aim was to determine if central pool cholesterol formation rate is related to apo E phenotype in healthy normolipidaemic males.


METHODS
Subjects consumed a fixed composition diet for 5 d and at 07:00 hours on d 5 drank 0.7 g deuterium oxide (D2O).kg-1 body water. Over d 5 body water deuterium enrichment was maintained by ingestion of labelled drinking water. The fractional synthetic rate of the central pool free cholesterol was determined over two consecutive 12 h intervals by the incorporation of deuterium from body water into plasma unesterified cholesterol.


METHODS
Participants were healthy male volunteers, mean age 26.4 years. They were divided into E2/(2 or 3) and E4/(4 or 3) alleles, n = 9 in each group.


RESULTS
Subjects with E2/- showed lower fractional synthetic rates than E4/- subjects, at 0.070(SEM 0.007) v 0.097(0.009) d-1 over the 24 h period (p less than 0.05). Cholesterol fractional synthetic rate was higher during the night than during the day (p less than 0.05).


CONCLUSIONS
These findings suggest an increased central pool free cholesterol synthesis in individuals possessing the apo epsilon-4 versus epsilon-2 allele. Apo E related regulation of whole body de novo cholesterol synthesis may therefore contribute to observed variations in plasma cholesterol levels.
Roe
R P
RP
University of British Columbia, Vancouver, Canada.
Jones
P J
PJ
Frohlich
J J
JJ
Schoeller
D A
DA
D000328:Adult; D000483:Alleles; D001057:Apolipoproteins E / Q000235:genetics*; D002784:Cholesterol / Q000096:biosynthesis* / Q000097:blood; D003903:Deuterium; D006801:Humans; D008297:Male; D010641:Phenotype; D011110:Polymorphism, Genetic
D001057:Apolipoproteins E; D002784:Cholesterol; D003903:Deuterium