Association between apolipoprotein E phenotype and endogenous cholesterol synthesis as measured by deuterium uptake.

Roe RP, Jones PJ, Frohlich JJ, Schoeller DA

Cardiovascular research

Mar 1, 1991

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Abstract

STUDY OBJECTIVE: The aim was to determine if central pool cholesterol formation rate is related to apo E phenotype in healthy normolipidaemic males. DESIGN: 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. SUBJECTS: 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. MEASUREMENTS AND MAIN 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.