Abstract/Summary

Background: Previous acute studies suggest the Glu298Asp polymorphism (rs1799983) may influence vascular reactivity in response to long-chain n-3 polyunsaturated fat (PUFA) intake. However, the effects of this genotype on postprandial vascular function following meals rich in saturated (SFA), n-6 PUFA and monounsaturated (MUFA) fats are unclear. Objective: 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. Methods: In a randomized, double-blind, cross-over, acute study, 32 postmenopausal women (mean±SD age 58±5 y; BMI 25.9±4.1 kg/m2) consumed mixed meals (breakfast: 0 min, 50 g fat; lunch: 330 min, 30 g fat) containing SFA, n-6 PUFA or MUFA 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 480 min after breakfast. Participants were retrospectively genotyped for the Glu298Asp (rs1799983) polymorphism. Data were analysed using linear mixed models. Results: For the postprandial %FMD response, a test fat x genotype interaction was observed for the area under the curve (AUC; P=0.019) but not incremental AUC, with the AUC being ~24% greater after MUFA than SFA and n-6 PUFA-rich meals in the Glu298 homozygotes (P≤0.026). Test fat x genotype interactions were also evident for postprandial insulin (P≤0.005), with the MUFA-rich meals demonstrating significantly higher AUC (12.8%/14.9%), incremental AUC (14.6%/20.0%) and maximum concentration (20.0%/34.5%) versus 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. Conclusion: 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.