Influence of APOE-2 genotype on the relation between adiposity and plasma lipid levels in patients with vascular disease

BACKGROUND: Apolipoprotein E (APOE) genotypes are associated with different plasma lipid levels. People with the APO ε2 genotype can develop a disorder called dysbetalipoproteinemia (DBL). A possible predisposing factor for DBL is adiposity. We evaluated whether and to what extent the APOE genotype modifies the relation between adiposity and lipids in patients with manifest arterial disease and we looked at possible determinants of DBL in ε2 homo- and heterozygote patients. METHODS: This prospective cohort study was performed in 5450 patients with manifest arterial disease from the Secondary Manifestations of ARTerial disease (SMART) study. The APOE genotype was measured in all patients and revealed 58 ε2 homozygotes, 663 ε2 heterozygotes, 3181 ε3 homozygotes and 1548 ε4 carriers. The main dependent variable was non-high-density lipoprotein cholesterol (non-HDL-c). The relation between adiposity (including body mass index (BMI), waist circumference (waist), visceral adipose tissue (VAT) and metabolic syndrome (MetS)) and lipids was evaluated with linear regression analyses. Determinants of DBL were evaluated using logistic regression. RESULTS: There was significant effect modification by the APOE genotype on the relation between non-HDL-c and BMI, waist, VAT and MetS. There was an association between BMI and non-HDL-c in ε2 homozygotes (β 0.173, 95% confidence interval (CI) 0.031-0.314, P = 0.018) and ε4 carriers (β 0.033, 95% CI 0.020-0.046, P < 0.001). In all genotypes, there was an effect of waist, VAT and MetS on non-HDL-c, but these effects were most distinct in ε2 homozygotes (waist β 0.063, 95% CI 0.015-0.110, P = 0.011; VAT β 0.580, 95% CI 0.270-0.889, P = 0.001; MetS β 1.760, 95% CI 0.668-2.852, P = 0.002). Determinants of DBL in ε2 homo- and heterozygotes were VAT and MetS. CONCLUSION: The APOE genotype modifies the relation between adiposity and plasma lipid levels in patients with vascular disease. The relation between adiposity and lipids is present in all patients, but it is most distinct in ε2 homozygote patients. Abdominal fat and MetS are determinants of DBL.