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

Abstract

Apolipoprotein (APO) E (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 APOE genotype and cardiometabolic risk markers in response to acute and chronic dietary fat intakes. Associations with fasting (baseline) outcome measures (n = 218) were determined using data from the chronic DIVAS (n = 191/195 adults at moderate cardiovascular disease risk) and acute DIVAS-2 (n = 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 APOE (rs429358, rs7412). For baseline cardiometabolic outcomes, E4 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 E3/E3 and E2 carriers (p ≤ 0.003). Digital volume pulse stiffness index was higher in E2 carriers than the E3/E3 group (p = 0.011). Following chronic dietary fat intake, the significant diet × genotype interaction was found for fasting triacylglycerol (p = 0.010), with indication of a differential responsiveness to MUFA intake between the E3/E3 and E4 carriers (p = 0.006). Test fat × genotype interactions were observed for the incremental area under the curve for the postprandial apolipoprotein B (apoB; p = 0.022) and digital volume pulse reflection index (DVP-RI; p = 0.030) responses after the MUFA-rich meals, with a reduction in E4 carriers and increase in the E3/E3 group for the apoB response, but an increase in E4 carriers and decrease in the E3/E3 group for the DVP-RI response. In conclusion, baseline associations between the APOE 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 APOE genotype on cardiometabolic markers in the acute and chronic state requires confirmation.

<p>Impact of <em>APOE</em> Alleles-by-Diet Interactions on Glycemic and Lipid Features– A Cross-Sectional Study of a Cohort of Type 2 Diabetes Patients from Western Mexico: Implications for Personalized Medicine</p>

“… 37 Also, a differential responsiveness of fasting TG to MUFA intake was found, with an increase and decrease in TG concentrations in APOE ε3 and APOE ε4 carriers, respectively. 38 However, no statistically significant interactions were observed between APOE alleles and SFA intake concerning TC and LDL-c levels in a Lithuanian adult population. 39 Additionally, no relevant interactions between APOE SNPs/haplotypes and dietary factors with plasma lipids were found after correction for multiple testing in two different cohorts.…”

Effect of fat-reformulated dairy food consumption on postprandial flow-mediated dilatation and cardiometabolic risk biomarkers compared with conventional dairy: a randomized controlled trial

“…However, the FA composition of the background diet can also influence postprandial cardiometabolic responses and may be of greater importance to long-term health than isolated (acute) dietary FA exposures ( 9 ). Furthermore, genetic makeup has also been shown to impact postprandial cardiometabolic disease risk markers ( 10–12 ), with APOE4 allele or endothelial NO synthase ( eNOS ) Glu298Asp (rs1799983) polymorphism found to be responsive to the replacement of meal SFAs with cis -MUFAs ( 13 , 14 ). However, the impact of these genotypes on postprandial cardiometabolic risk outcomes in response to changes in habitual FA intake is unclear.…”

Nutrigenomics of Dietary Lipids

“…In the same way, in the Food4Me study, the ε4 allele was associated with higher total cholesterol compared to non-risk genotypes [161]. Additionally, a 16-week dietary intervention with a replacement of 9.5% energy of MUFAs or ω-6 FAs, reduced plasmatic CRP levels in APOE ε4 carriers, while APOE ε3/ε3 carriers showed an opposite increment in CRP concentration [163].…”