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

BackgroundConsumption 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.MethodsThe 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.ResultsAfter 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.ConclusionsIn 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.Trial registrationThe trial was registered at www.clinicaltrials.gov as NCT01478958.Electronic supplementary materialThe online version of this article (10.1186/s12944-017-0606-3) contains supplementary material, which is available to authorized users.

Common Genetic Variations Involved in the Inter-Individual Variability of Circulating Cholesterol Concentrations in Response to Diets: A Narrative Review of Recent Evidence

“…Apolipoprotein E is one of the major proteins involved in the transport of cholesterol and TG within the circulation [ 53 ]. A 2017 retrospective analysis of 120 participants enrolled in the DIVAS study, a parallel design based on a food-exchange model of SFA, monounsaturated fatty acid (MUFA), and polyunsaturated fatty acid (PUFA) intakes in free-living individuals for 16 wk, reported that only APOE rs1064725-TT homozygotes, but not G allele carriers, showed a reduction in serum TC concentrations after the MUFA diet (−0.71 ± 1.88 mmol/L) compared to the SFA (0.34 ± 0.55 mmol/L) or n-6 PUFA diets (−0.08 ± 0.73 mmol/L) [ 23 ]. A German diabetes study evaluated the interaction between dietary patterns, using FFQ data, and APOE polymorphisms in 348 diabetic patients, where among carriers of the APOE ε2 isoform (E2/E2, E2/E3; rs429258: TT, rs7412: TT/CT), lower versus higher consumption frequencies of butter, cream cake, French fries, or alcoholic beverages were independently associated with a 40% reduction in serum LDL-C concentrations [ 24 ].…”

Personalised nutrition – phenotypic and genetic variation in response to dietary intervention

“…For example, Shatwan et al . (18) examined the impact of diets high in SFA, MUFA or n -6 PUFA over 16 weeks. Stratifying for ApoE SNP (rs1064725), they reported that only TT homozygotes showed a significant reduction in total cholesterol after the MUFA diet compared to the SFA or n -6 PUFA diets (18) .…”

“…(18) examined the impact of diets high in SFA, MUFA or n -6 PUFA over 16 weeks. Stratifying for ApoE SNP (rs1064725), they reported that only TT homozygotes showed a significant reduction in total cholesterol after the MUFA diet compared to the SFA or n -6 PUFA diets (18) . However, one must remember that whilst a study may be examining impact of genotype, that this may not be the only factor influencing response, for example, Caslake et al .…”

Hazelnuts as Source of Bioactive Compounds and Health Value Underestimated Food

“…14,15 From the nutritional viewpoint, various studies have confirmed that a diet with a low amount of saturated fatty acids and high content of MUFA can effectively reduce the risk of coronary heart disease amending blood lipid levels and blood pressure ameliorating metabolic syndrome and insulin sensitivity. [18][19][20][21]…”