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Apolipoprotein E gene polymorphism modifies fasting total cholesterol concentrations in response to replacement of dietary saturated with monounsaturated fatty acids in adults at moderate cardiovascular disease risk.

ABSTRACT: Consumption of ?10% total energy from fat as saturated fatty acids (SFA) is recommended for cardiovascular disease risk reduction in the UK; however there is no clear guidance on the optimum replacement nutrient. Lipid-associated single-nucleotide polymorphisms (SNPs) have been shown to modify the lipid responses to dietary fat interventions. Hence, we performed a retrospective analysis in 120 participants from the Dietary Intervention and VAScular function (DIVAS) study to investigate whether lipoprotein lipase (LPL) and apolipoprotein E (APOE) SNPs modify the fasting lipid response to replacement of SFA with monounsaturated (MUFA) or n-6 polyunsaturated (PUFA) fatty acids.The DIVAS study was a randomized, single-blinded, parallel dietary intervention study performed in adults with a moderate cardiovascular risk who received one of three isoenergetic diets rich in SFA, MUFA or n-6 PUFA for 16 weeks.After the 16-week intervention, a significant diet-gene interaction was observed for changes in fasting total cholesterol (P?=?0.001). For the APOE SNP rs1064725, only TT homozygotes showed a significant reduction in total cholesterol after the MUFA diet (n?=?33; -0.71?±?1.88 mmol/l) compared to the SFA (n?=?38; 0.34?±?0.55 mmol/l) or n-6 PUFA diets (n?=?37; -0.08?±?0.73 mmol/l) (P?=?0.004). None of the interactions were statistically significant for the other SNPs.In summary, our findings have demonstrated a greater sensitivity of the APOE SNP rs1064725 to dietary fat composition, with a total cholesterol lowering effect observed following substitution of SFA with MUFA but not n-6 PUFA. Further large intervention studies incorporating prospective genotyping are required to confirm or refute our findings.The trial was registered at www.clinicaltrials.gov as NCT01478958.

SUBMITTER: Shatwan IM

PROVIDER: S-EPMC5701425 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature

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Apolipoprotein E gene polymorphism modifies fasting total cholesterol concentrations in response to replacement of dietary saturated with monounsaturated fatty acids in adults at moderate cardiovascular disease risk.

Shatwan Israa M IM Weech Michelle M Jackson Kim G KG Lovegrove Julie A JA Vimaleswaran Karani S KS

Lipids in health and disease 20171123 1

<h4>Background</h4>Consumption of ≤10% total energy from fat as saturated fatty acids (SFA) is recommended for cardiovascular disease risk reduction in the UK; however there is no clear guidance on the optimum replacement nutrient. Lipid-associated single-nucleotide polymorphisms (SNPs) have been shown to modify the lipid responses to dietary fat interventions. Hence, we performed a retrospective analysis in 120 participants from the Dietary Intervention and VAScular function (DIVAS) study to in ...[more]

PMID: 29169396

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Project description:BackgroundModifying dairy fat composition by increasing the MUFA content is a potential strategy to reduce dietary SFA intake for cardiovascular disease (CVD) prevention in the population.ObjectivesTo determine the effects of consuming SFA-reduced, MUFA-enriched (modified) dairy products, compared with conventional dairy products (control), on the fasting cholesterol profile (primary outcome), endothelial function assessed by flow-mediated dilatation (FMD; key secondary outcome), and other cardiometabolic risk markers.MethodsA double-blind, randomized, controlled crossover 12-wk intervention was conducted. Participants with a 1.5-fold higher (moderate) CVD risk than the population mean replaced habitual dairy products with study products (milk, cheese, and butter) to achieve a high-fat, high-dairy isoenergetic daily dietary exchange [38% of total energy intake (%TE) from fat: control (dietary target: 19%TE SFA; 11%TE MUFA) and modified (16%TE SFA; 14%TE MUFA) diet].ResultsFifty-four participants (57.4% men; mean ± SEM age: 52 ± 3 y; BMI: 25.8 ± 0.5 kg/m2) completed the study. The modified diet attenuated the rise in fasting LDL cholesterol observed with the control diet (0.03 ± 0.06 mmol/L and 0.19 ± 0.05 mmol/L, respectively; P = 0.03). Relative to baseline, the %FMD response increased after the modified diet (0.35% ± 0.15%), whereas a decrease was observed after the control diet (-0.51% ± 0.15%; P< 0.0001). In addition, fasting plasma nitrite concentrations increased after the modified diet, yet decreased after the control diet (0.02 ± 0.01 μmol/L and -0.03 ± 0.02 μmol/L, respectively; P = 0.01).ConclusionsIn adults at moderate CVD risk, consumption of a high-fat diet containing SFA-reduced, MUFA-enriched dairy products for 12 wk showed beneficial effects on fasting LDL cholesterol and endothelial function compared with conventional dairy products. Our findings indicate that fatty acid modification of dairy products may have potential as a public health strategy aimed at CVD risk reduction. This trial was registered at clinicaltrials.gov as NCT02089035.

Project description:BackgroundChronic consumption of dairy products with an SFA-reduced, MUFA-enriched content was shown to impact favorably on brachial artery flow-mediated dilatation (FMD). However, their acute effect on postprandial cardiometabolic risk biomarkers requires investigation.ObjectiveThe effects of sequential high-fat mixed meals rich in fatty acid (FA)-modified or conventional (control) dairy products on postprandial FMD (primary outcome) and systemic cardiometabolic biomarkers in adults with moderate cardiovascular risk (≥50% above the population mean) were compared.MethodsIn a randomized crossover trial, 52 participants [mean ± SEM age: 53 ± 2 y; BMI (kg/m2) 25.9 ± 0.5] consumed a high-dairy-fat breakfast (0 min; ∼50 g total fat: modified: 25 g SFAs, 20 g MUFAs; control: 32 g SFAs, 12 g MUFAs) and lunch (330 min; ∼30 g total fat; modified: 15 g SFAs, 12 g MUFAs; control: 19 g SFAs, 7 g MUFAs). Blood samples were obtained before and until 480 min after breakfast, with FMD assessed at 0, 180, 300, and 420 min. Data were analyzed by linear mixed models.ResultsPostprandial changes in cardiometabolic biomarkers were comparable between the different dairy meals, with the exception of a tendency for a 4% higher AUC for the %FMD response following the modified-dairy-fat meals (P = 0.075). Plasma total lipid FA analysis revealed that incremental AUC responses were 53% lower for total SFAs, 214% and 258% higher for total cis-MUFAs (predominantly cis-9 18:1), and trans-18:1, respectively, following the modified relative to the control dairy meals (all P < 0.0001).ConclusionsIn adults at moderate cardiovascular risk, acute consumption of sequential high-fat meals containing FA-modified dairy products had little impact on postprandial endothelial function or systemic cardiometabolic biomarkers, but a differential effect on the plasma total lipid FA profile, relative to conventional dairy fat meals.This trial was registered at clinicaltrials.gov as NCT02089035.

Dataset Information

Apolipoprotein E gene polymorphism modifies fasting total cholesterol concentrations in response to replacement of dietary saturated with monounsaturated fatty acids in adults at moderate cardiovascular disease risk.

Publications

Apolipoprotein E gene polymorphism modifies fasting total cholesterol concentrations in response to replacement of dietary saturated with monounsaturated fatty acids in adults at moderate cardiovascular disease risk.

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