ApoCIII gene variants modulate postprandial response to both glucose and fat tolerance tests.
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.


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.
Waterworth
D M
DM
Division of Cardiovascular Genetics, Department of Medicine, The Rayne Institute, University College London, UK. rmhadw@ucl.ac.uk
Ribalta
J
J
Nicaud
V
V
Dallongeville
J
J
Humphries
S E
SE
Talmud
P
P
D000293:Adolescent; D000328:Adult; D000483:Alleles; D053305:Apolipoprotein C-III; D001056:Apolipoproteins C / Q000235:genetics*; D004041:Dietary Fats / Q000494:pharmacology*; D004435:Eating / Q000502:physiology*; D005787:Gene Frequency; D008040:Genetic Linkage / Q000235:genetics; D014644:Genetic Variation / Q000502:physiology*; D005947:Glucose / Q000502:physiology*; D005951:Glucose Tolerance Test; D006801:Humans; D008297:Male; D014280:Triglycerides / Q000097:blood
D053305:Apolipoprotein C-III; D001056:Apolipoproteins C; D004041:Dietary Fats; D014280:Triglycerides; D005947:Glucose