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ORIGINAL RESEARCH COMMUNICATION |
1 From the Department of Nutritional Sciences, Faculty of Medicine, University of Toronto (PDND and TMSW); the Blackburn Cardiovascular Genetics Laboratory, Robarts Research Institute, London, Canada (RAH); and the Division of Endocrinology and Metabolism, St Michael's Hospital, Toronto (TMSW).
Background: The alanine-for-threonine substitution at codon 54 (A54T polymorphism) in the fatty acid-binding protein 2 gene (FABP2) has been associated with hypertriglyceridemia and insulin resistance. Obese and diabetic T54 carriers have greater postprandial lipemia than do A54 homozygotes. The T54 protein isoform is also associated with increased triacylglycerol secretion in vitro.
Objective: We investigated diet-gene interactions by measuring postprandial lipids, glucose, insulin, and C-peptide in healthy, nonobese A54 homozygotes and T54 carriers after ingestion of 3 different fats.
Design: Eleven A54 homozygotes and 11 T54 carriers were given 3 oral-fat-tolerance tests (butter, safflower oil, and olive oil). Cholesterol and triacylglycerol were measured in plasma and in chylomicron fractions.
Results: There was no main effect of FABP2 genotype for chylomicron triacylglycerol, glucose, or C-peptide. The area under the insulin curve and the ratio of insulin to C-peptide were lower in T54 carriers than in A54 homozygotes [312 ± 29 (
± SEM) compared with 425 ± 31 pmol · h/L (P = 0.05) and 0.23 ± 0.03 compared with 0.40 ± 0.05 (P = 0.04), respectively], which suggests greater hepatic insulin clearance in T54 carriers. An association between genotype and chylomicron cholesterol was seen only after olive oil: values were higher (P = 0.02) in T54 carriers (0.087 ± 0.006 mmol · h/L) than in A54 homozygotes (0.058 ± 0.004 mmol · h/L). The main effect of fat was significant for the areas under the chylomicron cholesterol and chylomicron triacylglycerol curves [higher values for safflower (0.635 ± 0.053 and 2.48 ± 0.30 mmol · h/L, respectively) and olive (0.592 ± 0.052 and 2.48 ± 0.32 mmol · h/L, respectively) oils than for butter (0.425 ± 0.043 and 1.69 ± 0.20 mmol · h/L, respectively); P < 0.05].
Conclusions: The A54T polymorphism results in a diet-gene interaction: the T54 group had increased chylomicron cholesterol after olive oil only. Nevertheless, the greater hepatic insulin clearance in T54 carriers suggests that the polymorphism may not be deleterious in nonobese subjects.
Key Words: Fatty acid-binding protein 2 gene • intestinal fatty acid-binding protein • postprandial lipids • dietary fat • chylomicrons • glucose • insulin • C-peptide
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