Waterworth, DM; Ribalta, J; Nicaud, V; Dallongeville, J; Humphries, SE; Talmud, P; EARS Grp,; (1999) ApoCIII gene variants modulate postprandial response to both glucose and fat tolerance tests. CIRCULATION , 99 (14) 1872 - 1877.
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Background-We investigated the relationship between variation in the apolipoprotein (apo) AI-CIII-AIV gene cluster and response to an oral glucose test (OGTT) and oral fat load test (OFPT) in the EARSII group of young, healthy male offspring whose fathers had had a myocardial infarction before the age of 55 years (cases, n=407) compared with age-matched controls (n=415). The apoCIII variations examined were C3238G (SstI) in the 3'-UTR, C1100T in exon 3, C-482T in the insulin response element (IRE), and T-2854G in the apoCIII-AIV intergenic region.Methods and Results-The postprandial response was regulated by variation at the T-2854G and C3238G sites. After the OFTT, carriers of the rare alleles had delayed clearance of triglyceride (Tg) levels; G-2854 carriers showed the largest effect on Tg (AUC, 24%; greater, P<0.002; peak, 19% greater, P<0.005), and G3238 carriers showed a smaller response (AUC, 13% greater, P<0.05; peak, 13% greater, P=0.03). However, after adjustment for fasting level of Tg, only the effect with the T-2854G remained significant. Variation at the C-482T (IRE) determined response to the OGTT, with carriers of the rare T-482 having significantly elevated glucose (28.7% AUG, P=0.013) and insulin (20.5% AUG, P<0.01) concentrations.Conclusions-These data suggest that specific genetic variants at the apoCIII gene locus differentially affect postprandial and response to OGTT and suggest a novel mechanism for the effects of variation at this locus on risk for atherosclerosis.
|Title:||ApoCIII gene variants modulate postprandial response to both glucose and fat tolerance tests|
|Keywords:||genes, apolipoproteins, diet, RETINYL PALMITATE RESPONSES, APOLIPOPROTEIN-C-III, MIDDLE-AGED MEN, APO-CIII, LIPOPROTEIN-LIPASE, TRANSGENIC MICE, A-I, HYPERTRIGLYCERIDEMIA, ATHEROSCLEROSIS, TRIGLYCERIDE|
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