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Background  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.    Methods  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.    Results  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.    Conclusions  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.    Trial registration  The trial was registered at  www.clinicaltrials.gov  as NCT01478958.    Electronic supplementary material  The online version of this article (10.1186/s12944-017-0606-3) contains supplementary material, which is available to authorized users.

lipids in health and disease

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