Apolipoprotein E genotype, lifestyle and coronary artery disease: Gene-environment interaction analyses in the UK Biobank population

Background and aims: The APOE ε4 genotype has a higher risk for developing coronary artery disease (CAD), but there is preliminary evidence that antioxidative lifestyle factors interact with APOE genotype on CAD risk. Here, we assessed the effect modification of physical activity, oily fish and polyunsaturated fatty acid (PUFA) intake with APOE genotype on risk of incident CAD.

Methods: The present study comprised 345,659 white European participants from UK Biobank (mean age: 56.5 years, 45.7% men) without a history of CAD. Information regarding physical activity, oily fish intake and PUFA intake was collected through questionnaires, and information on incident CAD through linkage with hospital admission records. Analyses were performed using Cox proportional hazard models adjusted for age and sex.

Results: Higher physical activity level and oily fish intake were both associated with a lower incidence of CAD. However, these associations were similar across the different APOE genotypes (p-values for interaction > 0.05). Most notable, higher PUFA intake was associated with a lower CAD risk in APOE ε4 genotype carriers (hazard ratio: 0.76, 95% confidence interval: 0.63-0.92), and not in APOE ε3/ε3 genotype carriers (0.90; 0.79, 1.02), but without statistical evidence for effect modification (p-value_interaction = 0.137).

Conclusions: While higher physical activity and high fish and PUFA intake were associated with a lower risk of incident CAD, no evidence for interaction of these lifestyle factors with APOE genotype was observed in UK Biobank participants. Interventions intended to reduce cardiovascular risk might therefore be similarly effective across the APOE genotype carriers.