The APOLIPOPROTEIN E genotype impacts on the responsiveness of fasting lipids and gut peptides to functional interventions - findings from the CABALA study

Beneficial effects of dietary fibres, polyphenols, and probiotics (referred to as functional interventions) on cardiometabolic health may be mediated by changes in gut microbiota composition leading to reductions in low-density lipoprotein cholesterol (LDL-C) concentration⁽¹⁾. The APOLIPOPROTEIN (APO)E genotype has been shown to impact on the responsiveness of the fasting lipid profile and cardiovascular disease risk to dietary fat intake. However, little is known about other nutrient-gene interactions, with one study reporting a greater LDL-C lowering effect in APOE4 carriers than wild- type APOE3/E3 group after chronic intake of plant sterols⁽²⁾. Our aim was to investigate the association of the APOE genotype with fasting cardiometabolic disease risk markers following chronic consumption of functional interventions known to impact on the gut microbiota.

In this secondary analysis from the CABALA study⁽³⁾, data for participants assigned to the oats, apples and probiotic interventions (n = 46/61, mean ± SD, age 52 ± 11y and BMI 24.9 ± 3.1kg/m²), were combined. In brief, healthy volunteers [randomised based on age, sex, BMI and serum total cholesterol (TC)] were assigned to one of three interventions: two placebo capsules and i) 40g/day of porridge oats (n = 14) or ii) two Renetta Canada apples/day (n = 16), or iii) two Lactobacillus reuteri capsules with 40g/day of cornflakes (n = 15) for 8 weeks. At weeks 0 and 8, a fasting blood sample was taken for the measurement of the lipid profile, glucose and gut peptides. APOE genotyping was performed retrospectively (rs429358 and rs7412) [E2 carriers (E2/E2 and E2/E3, n = 7), E3/E3 group (wild-type, n = 28) and E4 carriers (E3/E4 and E4/E4, n = 10)]. A linear mixed-model was used to determine the impact of genotype on the cardiometabolic outcomes in response to the functional interventions.

Prior to the start of the interventions (week 0), fasting LDL-C concentrations were higher in E4 carriers compared with the E3/E3 group and E2 carriers (p£0.026) TC) concentrations were also higher in the E4 carriers than E3/E3 group (p = 0.034), with a tendency for a similar effect evident on apoB and non- high-density lipoprotein-cholesterol (p = 0.051–0.078) concentrations. Following the chronic interventions, significant visit*genotype interactions were found for fasting TC, LDL-C, apoB, glucose and peptide YY (PYY)(p£0.032). Relative to week 0, there was a reduction in TC, LDL-C and apoB at week 8 in the E4 carriers whereas there was an increase in glucose and PYY in the E2 carriers, relative to the other genotype groups.

In conclusion, baseline associations between the APOE genotype and fasting lipids confirm previous findings. Data from our exploratory analyses indicate that APOE genotype had an impact on fasting cardiometabolic risk markers in response to daily consumption of the functional interventions. Further studies are needed to confirm these associations.