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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.

SUBMITTER: Griffin BA

PROVIDER: S-EPMC6213759 | biostudies-other | 2018 Oct

REPOSITORIES: biostudies-other

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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.

Griffin Bruce A BA Walker Celia G CG Jebb Susan A SA Moore Carmel C Frost Gary S GS Goff Louise L Sanders Tom A B TAB Lewis Fiona F Griffin Margaret M Gitau Rachel R Lovegrove Julie A JA

Nutrients 20181017 10

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 retrospe ...[more]

PMID: 30336580

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Project description:BackgroundThe associations between dietary saturated fats and the risk of coronary heart disease (CHD) remain controversial, but few studies have compared saturated with unsaturated fats and sources of carbohydrates in relation to CHD risk.ObjectivesThis study sought to investigate associations of saturated fats compared with unsaturated fats and different sources of carbohydrates in relation to CHD risk.MethodsWe followed 84,628 women (Nurses' Health Study, 1980 to 2010), and 42,908 men (Health Professionals Follow-up Study, 1986 to 2010) who were free of diabetes, cardiovascular disease, and cancer at baseline. Diet was assessed by a semiquantitative food frequency questionnaire every 4 years.ResultsDuring 24 to 30 years of follow-up, we documented 7,667 incident cases of CHD. Higher intakes of polyunsaturated fatty acids (PUFAs) and carbohydrates from whole grains were significantly associated with a lower risk of CHD comparing the highest with lowest quintile for PUFAs (hazard ratio [HR]: 0.80, 95% confidence interval [CI]: 0.73 to 0.88; p trend <0.0001) and for carbohydrates from whole grains (HR: 0.90, 95% CI: 0.83 to 0.98; p trend = 0.003). In contrast, carbohydrates from refined starches/added sugars were positively associated with a risk of CHD (HR: 1.10, 95% CI: 1.00 to 1.21; p trend = 0.04). Replacing 5% of energy intake from saturated fats with equivalent energy intake from PUFAs, monounsaturated fatty acids, or carbohydrates from whole grains was associated with a 25%, 15%, and 9% lower risk of CHD, respectively (PUFAs, HR: 0.75, 95% CI: 0.67 to 0.84; p < 0.0001; monounsaturated fatty acids, HR: 0.85, 95% CI: 0.74 to 0.97; p = 0.02; carbohydrates from whole grains, HR: 0.91, 95% CI: 0.85 to 0.98; p = 0.01). Replacing saturated fats with carbohydrates from refined starches/added sugars was not significantly associated with CHD risk (p > 0.10).ConclusionsOur findings indicate that unsaturated fats, especially PUFAs, and/or high-quality carbohydrates can be used to replace saturated fats to reduce CHD risk.

Project description:BACKGROUND:Walnuts have established lipid-/lipoprotein-lowering properties; however, their effect on lipoprotein subclasses has not been investigated. Furthermore, the mechanisms by which walnuts improve lipid/lipoprotein concentrations are incompletely understood. OBJECTIVES:We aimed to examine, as exploratory outcomes of this trial, the effect of replacing SFAs with unsaturated fats from walnuts or vegetable oils on lipoprotein subclasses, cholesterol efflux, and proprotein convertase subtilisin/kexin type 9 (PCSK9). METHODS:A randomized, crossover, controlled-feeding study was conducted in individuals at risk of cardiovascular disease (CVD) (n = 34; 62% men; mean ± SD age 44 ± 10 y; BMI: 30.1 ± 4.9 kg/m2). After a 2-wk run-in diet (12% SFAs, 7% PUFAs, 12% MUFAs), subjects consumed the following diets, in randomized order, for 6 wk: 1) walnut diet (WD) [57-99 g/d walnuts, 7% SFAs, 16% PUFAs [2.7% α-linolenic acid (ALA)], 9% MUFAs]; 2) walnut fatty acid-matched diet [7% SFAs, 16% PUFAs (2.6% ALA), 9% MUFAs]; and 3) oleic acid replaces ALA diet (ORAD) [7% SFAs, 14% PUFAs (0.4% ALA); 12% MUFAs] (all percentages listed are of total kilocalories ). Serum collected after the run-in (baseline) and each diet period was analyzed for lipoprotein classes and subclasses (vertical auto profile), cholesterol efflux, and PCSK9. Linear mixed models were used for data analysis. RESULTS:Compared with the ORAD, total cholesterol (mean ± SEM -8.9± 2.3 mg/dL; -5.1%; P < 0.001), non-HDL cholesterol (-7.4 ± 2.0 mg/dL; -5.4%; P = 0.001), and LDL cholesterol (-6.9 ± 1.9 mg/dL; -6.5%; P = 0.001) were lower after the WD; no other pairwise differences existed. There were no between-diet differences for HDL-cholesterol or LDL-cholesterol subclasses. Lipoprotein(a) [Lp(a)], cholesterol efflux, and PCSK9 were unchanged after the diets. CONCLUSIONS:In individuals at risk of CVD, replacement of SFAs with unsaturated fats from walnuts or vegetable oils improved lipid/lipoprotein classes, including LDL-cholesterol, non-HDL cholesterol, and total cholesterol, without an increase in Lp(a). These improvements were not explained by changes in cholesterol efflux capacity or PCSK9. This trial was registered at clinicaltrials.gov as NCT01235832.

Dataset Information

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.

Publications

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.

Similar Datasets

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