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Open AccessArticle

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

1
Department of Nutritional Sciences, University of Surrey, Guildford GU2 7WG, UK
2
Medical Research Council Human Nutrition Research, Elsie Widdowson Laboratory, Cambridge CB1 9NL, UK
3
Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford OX2 6GG, UK
4
Nutrition and Dietetic Research Group, Imperial College London, London W12 OHS, UK
5
Nutritional Sciences Division, Kings College London, London WC2R 2LS, UK
6
Hugh Sinclair Unit of Human Nutrition, University of Reading, Reading RG6 6AP, UK
*
Author to whom correspondence should be addressed.
On behalf of the RISCK Study Group.
Nutrients 2018, 10(10), 1524; https://doi.org/10.3390/nu10101524
Received: 31 August 2018 / Revised: 27 September 2018 / Accepted: 12 October 2018 / Published: 17 October 2018
(This article belongs to the Special Issue Diet, Lipid and Lipoprotein Metabolism and Human Health)
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. View Full-Text
Keywords: apolipoprotein E genotype; LDL cholesterol; polymorphism; saturated fat; ‘RISCK’ study apolipoprotein E genotype; LDL cholesterol; polymorphism; saturated fat; ‘RISCK’ study
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Griffin, B.A.; Walker, C.G.; Jebb, S.A.; Moore, C.; Frost, G.S.; Goff, L.; Sanders, T.A.B.; Lewis, F.; Griffin, M.; Gitau, R.; Lovegrove, J.A. 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. Nutrients 2018, 10, 1524.

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