APOE4 Genotype Exerts Greater Benefit in Lowering Plasma Cholesterol and Apolipoprotein B than Wild Type (E3/E3), after Replacement of Dietary Saturated Fats with Low Glycaemic Index Carbohydrates

Abstract

We examined the impact of APOE genotype on plasma lipids and glucose in a secondary analysis of data from a five-arm, randomised controlled, parallel dietary intervention trial (‘RISCK’ study), to investigate the impact of replacing saturated fatty acids (SFA) with either monounsaturated fat (MUFA) or carbohydrate of high or low glycaemic index (GI) on CVD risk factors and insulin sensitivity. We tested the impact of APOE genotype (carriage of E2 and E4 alleles versus E3/E3), determined retrospectively, on plasma lipids, lipoproteins and glucose homeostasis at baseline (n = 469), and on the change in these variables after 24 weeks of dietary intervention (n = 389). At baseline, carriers of E2 (n = 70), E4 (n = 125) and E3/E3 (n = 274) expressed marked differences in total plasma cholesterol (TC, p = 0.001), low density lipoprotein cholesterol (LDL-C, p < 0.0001), apolipoprotein B (apo B, p < 0.0001) and total to high density lipoprotein cholesterol ratio (TC:HDL-C, p = 0.002), with plasma concentrations decreasing in the order E4 > E3/E3 > E2. Following intervention, there was evidence of a significant diet x genotype interaction with significantly greater decreases in TC (p = 0.02) and apo B (p = 0.006) among carriers of E4 when SFA was replaced with low GI carbohydrate on a lower fat diet (TC −0.28 mmol/L p = 0.03; apo B −0.1 g/L p = 0.02), and a relative increase in TC (in comparison to E3/E3) when SFA was replaced with MUFA and high GI carbohydrates (TC 0.3 mmol/L, p = 0.03). Among carriers of E2 (compared with E3/E3) there was an increase in triacylglycerol (TAG) when SFA was replaced with MUFA and low GI carbohydrates 0.46 mmol/L p = 0.001). There were no significant interactions between APOE genotype and diet for changes in indices of glucose homeostasis. In conclusion, variations in APOE genotype led to differential effects on the lipid response to the replacement of SFA with MUFA and low GI carbohydrates.

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

“…In the present baseline analysis, the higher fasting TC and LDL-C concentrations, and TC: HDL-C and LDL-C:HDL-C ratios were more evident in E4 carriers than E2 carriers and the E3/E3 wild-type genotype group, which confirms previous studies [4,5,20,31,32,33]. A number of possible mechanisms could explain the higher fasting TC and LDL-C concentrations in E4 carriers [11].…”

“…Previous studies have reported polymorphisms in the APOE gene to be associated with increased postprandial triacylglycerol (TAG) responses [17,18,19]. The Reading, Imperial, Surrey, Cambridge and Kings (RISCK) study reported differential effects on the lipid response when SFA was replaced with MUFA and low glycaemic index carbohydrates after a 24-week dietary intervention with variations in the APOE genotype [20]. However, data is extremely limited on the impact of meal fatty acids on postprandial lipid and vascular outcomes according to the APOE genotype.…”

The SNPs rs429358 and rs7412 of APOE gene are association with cerebral infarction but not SNPs rs2306283 and rs4149056 of SLCO1B1 gene in southern Chinese Hakka population

“…Furthermore, this study found ɛ3 to be the most common allele of the APOE gene, accounting for 85.20%, which was consistent with most previous studies [37,38]. This indicates that the APOE allele frequencies in the Meizhou area are similar to those of the Chinese-Northeast [39], Chinese-Jiangsu Han [40] and Chinese-Kunming Han [41] areas, though the ɛ4 allele frequency in Meizhou is lower than that in Shanghai [42].…”

APOE Alleles and Diet in Brain Aging and Alzheimer’s Disease

“…Findings from this pilot trial, however, need to be replicated in a larger study, but they underscore the differential response by both APOE genotype and cognitive state to high-fat ingestion. These findings may be counter-intuitive given that APOE4 carriers have higher LDL-C levels and that saturated fat intake can modestly increase levels of LDL-C. Interestingly, APOE4 also modulates the effect of switching from a high-fat diet to a low-fat diet on plasma cholesterol levels: APOE4 carriers who switched from a high-fat diet to low fat and low glycemic index high carb diet had greater reductions in LDL-C (Griffin et al, 2018).…”