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.
Highlights
Consumption of ≤10% total energy from fat as saturated fatty acids (SFA) is recommended for cardiovascular disease risk reduction in the UK; there is no clear guidance on the optimum replacement nutrient
The inter-individual variability in fasting plasma lipid responses to dietary fat intake is high; evidence supports that this is influenced by lipid-associated single-nucleotide polymorphisms (SNPs) such as apolipoprotein E (APOE) and lipoprotein lipase (LPL) genotypes [8,9,10]
In the Dietary Intervention and VAScular function (DIVAS) study, the isoenergetic replacement of 9.5–9.6% total energy (TE) from SFA with cis monounsaturated fatty acids (MUFA) or n–6 polyunsaturated fatty acids (PUFA) for 16 weeks in 195 adults at moderate cardiovascular disease (CVD) risk resulted in significant reductions of 8.4% and 9.2%, respectively, in total cholesterol, and 11.3% and 13.6%, in low-density lipoprotein cholesterol (LDL-C), in the fasted state [6]
Summary
120 participants (mean age, 47 ± 9 years; BMI, 26.4 ± 4.0 kg/m2) were included. At 16 weeks, after adjustment for age, sex, ethnicity and baseline BMI, a significant interaction between the APOE SNP rs1064725 and dietary intervention (SFA vs MUFA vs n-6 PUFA) on changes in fasting total cholesterol (Pinteraction = 0.001) was observed (Fig. 1). We observed an interaction between LPL SNP rs320 and the dietary fat intervention (SFA vs MUFA vs n-6 PUFA) on changes in LDL-C concentrations after 16 weeks (Pinteraction = 0.005) (Table 5). In the n-6 PUFA diet group, the G allele carriers (n = 19) of the LPL SNP showed a reduction in LDL-C levels (−1.0 ± 2.51 mmol/l) compared to the TT genotype (n = 24; 0.91 ± 2.23 mmol/l) (Passociation = 0.007) This interaction was not statistically significant after correction for multiple testing. None of the other SNPs showed a significant interaction on changes in lipid concentrations after the 16-week dietary intervention (Additional file 1: Tables S1-S3)
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