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.

Bruce Griffin,Margaret Griffin,Tom Sanders,Celia Walker,Susan Jebb,Carmel Moore,Julie Lovegrove,Gary Frost,Louise Goff,Fiona Lewis,Rachel Gitau

doi:10.3390/nu10101524

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.

Highlights

The reduction of dietary saturated fatty acids (SFA) to decrease serum LDL-C has been the mainstay of dietary recommendations to reduce cardiovascular disease risk for over 30 years [1,2].the strength and consistency of the effect of reducing SFA on LDL-C is highly variable between individuals [3], and influenced by the nature of the substituting macronutrient, food source [4,5], and innate biological differences in the metabolic response to changes in the amount and quality of dietary fat [6,7].The common APOE polymorphism has been shown to account for up to 7% of variation in total serum cholesterol (TC) and LDL-C in populations [8]
Glucose concentrations were measured with a hexokinase assay (Dimension clinical chemistry system; Dade Behring, Milton Keynes, UK), insulin concentrations were measured with an electro-chemiluminescence immunoassay (Roche, Indianapolis, IN, USA) on a Roche Elecsys analyzer (Roche), and non-esterified fatty acid (NEFA) concentrations were measured with an enzymatic colorimetric assay (Roche Diagnostics, Penzber, Germany)
Of variation in TC and LDL-C, respectively. These associations were reflected in significant differences in TC (p = 0.001), LDL-C (p = 0.0001), apo B (p = 0.0001), and TC:HDL-C and apo B:apo A-I ratios (p = 0.002, p = 0.0001, respectively) between APOE genotypes, with all values decreasing in the order of allele carriage E4 > E3/E3 > E2 (Table 1)

Summary

Introduction

The reduction of dietary saturated fatty acids (SFA) to decrease serum LDL-C has been the mainstay of dietary recommendations to reduce cardiovascular disease risk for over 30 years [1,2].the strength and consistency of the effect of reducing SFA on LDL-C is highly variable between individuals [3], and influenced by the nature of the substituting macronutrient, food source [4,5], and innate biological differences in the metabolic response to changes in the amount and quality of dietary fat [6,7].The common APOE polymorphism has been shown to account for up to 7% of variation in total serum cholesterol (TC) and LDL-C in populations [8]. The reduction of dietary saturated fatty acids (SFA) to decrease serum LDL-C has been the mainstay of dietary recommendations to reduce cardiovascular disease risk for over 30 years [1,2]. The strength and consistency of the effect of reducing SFA on LDL-C is highly variable between individuals [3], and influenced by the nature of the substituting macronutrient, food source [4,5], and innate biological differences in the metabolic response to changes in the amount and quality of dietary fat [6,7]. The extent to which APOE genotype contributes to variation in LDL-C in response to the reduction of SFA is less clear.

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