Genetic modifiers of the Portfolio Diet Score and LDL cholesterol in young adults

The Portfolio Diet has demonstrated clinically meaningful reductions in LDL-C concentrations. Variations in ABCA1, ABCG8, APOA5, ANGPTL3, and APOC1 have also been associated with LDL-C and other blood lipid concentrations. The interaction between these genetic variations and the Portfolio Diet on LDL-C is unclear. Therefore, we examined whether variations in genes involved in lipid metabolism modify the association between the Portfolio Diet Score (PDS) and its components and LDL-C concentrations.

This cross-sectional analysis included 1490 young adults (mean age, 23±2years) from the Toronto Nutrigenomics and Health Study. Adherence to the Portfolio Diet was measured by the PDS and its individual components. Using a candidate gene approach, participants were genotyped for SNPs in ABCA1 (rs1883025), ABCG8 (rs6544713), APOA5 (rs662799), ANGPTL3 (rs10889353) and APOC1 (rs4420638). Multiple linear regressions examined gene-diet interactions with LDL-C. Higher PDS, intake of plant protein, nuts, and phytosterols and lower intake of saturated fat and cholesterol sources were associated with lower LDL-C (p < 0.05). ABCA1 rs1883025 genotype modified the association between the PDS and LDL-C (p < 0.01). A 1-point higher PDS was associated with lower LDL-C among those with the ABCA1 rs1883025 CC (β: -0.017 mmol/L [95% CI: -0.027, -0.007], p < 0.01) and TT (-0.034 mmol/L [-0.065, -0.003], p = 0.03) genotypes. ABCG8 rs6544713 T allele was associated with higher LDL-C (p = 0.002). ABCG8 rs6544713 genotype modified the association between plant protein (p = 0.02) and phytosterols (p = 0.01) with LDL-C. A 1-serving higher intake of plant protein (-0.314 mmol/L [-0.601, -0.028], p = 0.03) and phytosterol (-0.051 mmol/L [-0.101, -0.002], p = 0.04) sources was associated with lower LDL-C among those with the ABCG8 rs6544713 TT genotype.

In young adults, higher PDS and intake of its components showed favourable associations with LDL-C. Our findings suggest that ABCA1 rs1883025 and ABCG8 rs6544713 genotypes modify the association of the PDS, plant protein and phytosterols with LDL-C.