Interaction of apolipoprotein E genotype with smoking and physical inactivity on coronary heart disease risk in men and women

ObjectiveApolipoprotein E genotype (APOE) polymorphism affects lipid levels and coronary heart disease (CHD) risk. However, these associations may be modified by lifestyle factors. Therefore, we studied whether smoking, physical inactivity or overweight interact with APOE on cholesterol levels and CHD risk.MethodsCombining two Swedish case-control studies yielded 1735 CHD cases and 4654 population controls (3747 men, 2642 women). Self-reported questionnaire lifestyle data included smoking (ever [current or former regular] or never) and physical inactivity (mainly sitting leisure time). We obtained LDL cholesterol levels and APOE genotypes. CHD risk was modelled using logistic regression to obtain odds ratios (ORs) and 95% confidence intervals (CIs), adjusted for relevant covariates.ResultsSmoking interacted with APOE on CHD risk; adjusted ORs for ever versus never smoking were 1.45 (95% CI 1.00–2.10) in ?2 carriers, 2.25 (95% CI 1.90–2.68) in ?3 homozygotes and 2.37 (95% CI 1.85–3.04) in ?4 carriers. Female ?4 carriers had OR 3.62 (95% CI 2.32–5.63). The adjusted ORs for physical inactivity were 1.09 (95% CI 0.73–1.61), 1.34 (95% CI 1.12–1.61), and 1.79 (95% CI 1.38–2.30) in ?2, ?3?3 and ?4 groups, respectively. No interaction was seen between overweight and APOE for CHD risk, or between any lifestyle factor and APOE for LDL cholesterol levels.ConclusionThe APOE ?2 allele counteracted CHD risk from smoking in both genders, while the ?4 allele was seen to potentiate this risk mainly in women. Similar ?2 protection and ?4 potentiation was suggested for CHD risk from physical inactivity.