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

AbstractBackgroundCarriers of theAPOE ε4genotype have an increased risk for developing coronary artery disease (CAD), but there is preliminary evidence that lifestyle factors interact withAPOEgenotype on CAD risk. Here, we assessed the interactions of physical activity, oily fish intake and polyunsaturated fatty acid (PUFA) intake withAPOEgenotype on risk of incident cardiovascular disease in a large population of middle-aged individuals.Methods and ResultsThe present study was embedded in the UK Biobank population and comprised 344,092 European participants (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. From these analyses, higher physical activity level and a higher intake of oily fish were associated with a lower incidence of CAD. These associations were similar across all APOE isoform groups (p-values for interaction > 0.05). A higher PUFA intake was only associated with a lower CAD risk inAPOE ε4carriers (hazard ratio: 0.76, 95% confidence interval: 0.62,0.90), however, no statistically significant interaction was observed (p-valueinteraction= 0.137).ConclusionWhile higher physical activity, fish intake and PUFA intake all decreased the risk of CAD, no evidence for interaction of these lifestyle factors withAPOEgenotype was observed in UK Biobank participants. Interventions intended to reduce cardiovascular risk might therefore be similarly effective across the APOE isoform carriers.