title: Influence of APOE-2 genotype on the relation between adiposity and plasma lipid levels in patients with vascular disease.
abstract: BACKGROUND
  Apolipoprotein E (APOE) genotypes are associated with different plasma lipid levels. People with the APO ɛ2 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 ɛ2 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 ɛ2 homozygotes, 663 ɛ2 heterozygotes, 3181 ɛ3 homozygotes and 1548 ɛ4 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 ɛ2 homozygotes (β 0.173, 95% confidence interval (CI) 0.031-0.314, P=0.018) and ɛ4 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 ɛ2 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 ɛ2 homo- and heterozygotes were VAT and MetS.
  
  
  CONCLUSIONS
  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 ɛ2 homozygote patients. Abdominal fat and MetS are determinants of DBL.
authors.affiliation: Department of Vascular Medicine, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: C
authors.initials: C
authors.lastname: Koopal
authors.affiliation: Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Y
authors.initials: Y
authors.lastname: van der Graaf
authors.affiliation: 1] Division Heart and Lungs, Department of Cardiology, University Medical Center Utrecht, Utrecht, The Netherlands [2] Durrer Center for Cardiogenetic Research, ICIN-Netherlands Heart Institute, Utrecht, The Netherlands [3] Faculty of Population Health Sciences, Institute of Cardiovascular Science, University College London, London, UK.
authors.forename: F W
authors.initials: FW
authors.lastname: Asselbergs
authors.affiliation: Department of Vascular Medicine, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: J
authors.initials: J
authors.lastname: Westerink
authors.affiliation: Department of Vascular Medicine, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: F L J
authors.initials: FL
authors.lastname: Visseren
mesh_terms: D050154:Adiposity / Q000235:genetics; D053329:Apolipoprotein E2 / Q000235:genetics / Q000378:metabolism*; D050218:Body Fat Distribution; D015992:Body Mass Index; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006801:Humans; D006952:Hyperlipoproteinemia Type III / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D008055:Lipids / Q000097:blood* / Q000235:genetics; D008297:Male; D024821:Metabolic Syndrome / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D056128:Obesity, Abdominal / Q000235:genetics / Q000378:metabolism*; D011446:Prospective Studies; D014652:Vascular Diseases / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology
chemical_list: D053329:Apolipoprotein E2; D008055:Lipids