Impact of the (epsilon) Genotype on Cardiometabolic Risk Markers and Responsiveness to Acute and Chronic Dietary Fat Manipulation.

() (ε) genotype is considered to play an important role in lipid responses to dietary fat manipulation but the impact on novel cardiometabolic risk markers is unclear. To address this knowledge gap, we investigated the relationship between the genotype and cardiometabolic risk markers in response to acute and chronic dietary fat intakes. Associations with fasting (baseline) outcome measures ( = 218) were determined using data from the chronic DIVAS ( = 191/195 adults at moderate cardiovascular disease risk) and acute DIVAS-2 ( = 27/32 postmenopausal women) studies examining the effects of diets/meals varying in saturated, polyunsaturated and monounsaturated (MUFA) fatty acid composition. Participants were retrospectively genotyped for (rs429358, rs7412). For baseline cardiometabolic outcomes, carriers had higher fasting total and low-density lipoprotein-cholesterol (LDL-C), total cholesterol: high-density lipoprotein-cholesterol (HDL-C) and LDL-C: HDL-C ratios, but lower C-reactive protein (CRP) than and carriers ( ≤ 0.003). Digital volume pulse stiffness index was higher in carriers than the group ( = 0.011). Following chronic dietary fat intake, the significant diet × genotype interaction was found for fasting triacylglycerol ( = 0.010), with indication of a differential responsiveness to MUFA intake between the and carriers ( = 0.006). Test fat × genotype interactions were observed for the incremental area under the curve for the postprandial apolipoprotein B (apoB; = 0.022) and digital volume pulse reflection index (DVP-RI; = 0.030) responses after the MUFA-rich meals, with a reduction in carriers and increase in the group for the apoB response, but an increase in carriers and decrease in the group for the DVP-RI response. In conclusion, baseline associations between the genotype and fasting lipids and CRP confirm previous findings, although a novel interaction with digital volume pulse arterial stiffness was observed in the fasted state and differential postprandial apoB and DVP-RI responses after the MUFA-rich meals. The reported differential impact of the genotype on cardiometabolic markers in the acute and chronic state requires confirmation.