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(Circulation. 1999;99:1872-1877.)
© 1999 American Heart Association, Inc.

Clinical Investigation and Reports

ApoCIII Gene Variants Modulate Postprandial Response to Both Glucose and Fat Tolerance Tests

Dawn M. Waterworth, PhD, ; Josep Ribalta, PhD, ; Viviane Nicaud, MA, ; Jean Dallongeville, PhD, ; Steve E. Humphries, PhD, ; Philippa Talmud, PhD, ; on behalf of the EARS Group

From the Division of Cardiovascular Genetics, Department of Medicine, The Rayne Institute, University College London, UK (D.M.W., J.R., S.E.H., P.T.); Hospital Broussais, Paris, France (V.N.); and Institute Pasteur, Lille, France (J.D.).

Correspondence to Dawn M. Waterworth, PhD, Division of Cardiovascular Genetics, Department of Medicine, The Rayne Institute, University College London, WC1E 6JJ, UK. E-mail rmhadmw{at}ucl.ac.uk

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 (OFTT) 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% AUC, P=0.013) and insulin (20.5% AUC, 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.

Key Words: genes • apolipoproteins • diet

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