THE SSTI POLYMORPHISM OF THE APOLIPOPROTEIN C-III GENE DETERMINES THEINSULIN-RESPONSE TO AN ORAL-GLUCOSE-TOLERANCE TEST AFTER CONSUMPTION OF A DIET RICH IN SATURATED FATS

The S2 allele of the SstI polymorphism of the apolipoprotein (apo) C-I II gene has been associated with elevated triacylglycerol concentratio ns, high blood pressure, and increased risk of coronary artery disease , all of which are characteristic of an insulin-resistant state, To st udy the effect of this mutation on carbohydrate metabolism in healthy persons, we gave 41 male subjects 3 consecutive diets. The first was r ich in saturated fat [15% protein, 47% carbohydrate, 38% fat (20% satu rated)], the second was a National Cholesterol Education Program Step 1 diet [15% protein, 57% carbohydrate, 28% fat (<10% saturated)], and the last was rich in monounsaturated fat [15% protein, 47% carbohydrat e. 38% fat (22% monounsaturated, <10% saturated)]. At the end of each dietary period, subjects received an oral-glucose-tolerance test (OGTT ). Apo C-III genotype significantly affected basal glucose concentrati ons (P < 0.045) and insulin concentrations after the OGTT (P < 0.012), APOC3'S1/APOC3*S2 subjects (n = 13) had higher insulin concentration s after the OGTT than APOC3S1/APOC3*S1 subjects (n = 28) in the 3 per iods (diet I, P < 0.0004. diet 2. P < 0.01: diet 3: P < 0.008). Multip le regression analysis showed that this polymorphism predicted the ins ulin response to the OGTT (P < 0.031) and the difference between basal insulin concentrations and insulin concentrations after the OGTT (P < 0.002) with the saturated fat diet. In summary, our results suggest t hat the mutation in the apo C-III gene affects insulin response to an OGTT, which could result in reduced sensitivity to insulin, especially when persons consume diets rich in saturated fat.