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.
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.
Authors: Sophie Eichenbaum-Voline; Michael Olivier; Emma L Jones; Rossitza P Naoumova; Bethan Jones; Brian Gau; Hetal N Patel; Mary Seed; D John Betteridge; David J Galton; Edward M Rubin; James Scott; Carol C Shoulders; Len A Pennacchio Journal: Arterioscler Thromb Vasc Biol Date: 2003-10-09 Impact factor: 8.311
Authors: F Cardona; F J Tinahones; E Collantes; A Escudero; E García-Fuentes; F J Soriguer Journal: Ann Rheum Dis Date: 2004-04-28 Impact factor: 19.103
Authors: Humaira Rasheed; Amanda J Phipps-Green; Ruth Topless; Malcolm D Smith; Catherine Hill; Susan Lester; Maureen Rischmueller; Matthijs Janssen; Timothy L Jansen; Leo A Joosten; Timothy R Radstake; Philip L Riches; Anne-Kathrin Tausche; Frederic Lioté; Alexander So; Andre van Rij; Gregory T Jones; Sally P McCormick; Andrew A Harrison; Lisa K Stamp; Nicola Dalbeth; Tony R Merriman Journal: Rheumatology (Oxford) Date: 2016-04-18 Impact factor: 7.580