Glu298Asp (rs1799983) Polymorphism Influences Postprandial Vascular Reactivity and the Insulin Response to Meals of Varying Fat Composition in Postmenopausal Women: Findings from the Randomized, Controlled Dietary Intervention and VAScular function (DIVAS)-2 Study

Abstract

Previous acute studies suggest the Glu298Asp polymorphism (rs1799983) may influence vascular reactivity in response to long-chain n-3 PUFA intake. However, the effects of this genotype on postprandial vascular function after meals rich in SFAs, n-6 PUFAs, and MUFAs are unclear. This study determined the impact of the Glu298Asp polymorphism on changes in vascular function and cardiometabolic risk biomarkers in response to sequential meals of varying fat composition. In a randomized, double-blind, crossover, acute study, 32 postmenopausal women (mean±SD age: 58±5y; BMI: 25.9±4.1kg/m2) consumed mixed meals (breakfast: 0min, 50g fat; lunch: 330min, 30g fat) containing SFAs, n-6 PUFAs, or MUFAs on 3 occasions. Blood samples for cardiometabolic disease risk markers and real-time measures of vascular reactivity [including flow-mediated dilatation (FMD; primary outcome)] were collected/performed before and regularly for 480min after breakfast. Participants were retrospectively genotyped for the Glu298Asp (rs1799983) polymorphism. Data were analyzed using linear mixed models. For the postprandial %FMD response, a test fat × genotype interaction was observed for the AUC (P=0.019) but not incremental AUC (IAUC), with the AUC being ∼24% greater after MUFA- than after SFA- and n-6 PUFA-rich meals in the Glu298 homozygotes (P≤0.026). Test fat × genotype interactions were also evident for postprandial insulin (P≤0.005), with the MUFA-rich meals demonstrating significantly higher AUC (12.8%/14.9%), IAUC (14.6%/20.0%), and maximum concentration (20.0%/34.5%) than the SFA- and n-6 PUFA-rich meals, respectively, in Asp298 carriers (P<0.05). Genotype did not influence other study outcome measures in response to the test fats. Our findings suggest the Glu298Asp polymorphism may represent a potential determinant of the inter-individual variability in postprandial responsiveness of %FMD and insulin to acute meal fat composition in postmenopausal women. Further studies are required to confirm these observations.This trial was registered at clinicaltrials.gov as NCT02144454.