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Clinical Studies and Practice

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

International Journal of Obesity volume 39, pages 265–269 (2015)Cite this article

Subjects

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.

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 ɛ2 homozygote patients. Abdominal fat and MetS are determinants of DBL.

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Acknowledgements

We gratefully acknowledge the contribution of the SMART research nurses, R van Petersen (data-manager), H Pijl (vascular manager) and the members of the SMART Study Group: PA Doevendans, Department of Cardiology; A Algra; Y van der Graaf; DE Grobbee; GEHM Rutten, Julius Center for Health Sciences and Primary Care; LJ Kappelle, Department of Neurology; WPTM Mali, Department of Radiology; FL Moll, Department of Vascular Surgery; FLJ Visseren, Department of Vascular Medicine.

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Authors and Affiliations

  1. Department of Vascular Medicine, University Medical Center Utrecht, Utrecht, The Netherlands

    C Koopal, J Westerink & F L J Visseren

  2. Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands

    Y van der Graaf

  3. Division Heart and Lungs, Department of Cardiology, University Medical Center Utrecht, Utrecht, The Netherlands

    F W Asselbergs

  4. Durrer Center for Cardiogenetic Research, ICIN-Netherlands Heart Institute, Utrecht, The Netherlands

    F W Asselbergs

  5. Faculty of Population Health Sciences, Institute of Cardiovascular Science, University College London, London, UK

    F W Asselbergs

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  1. C Koopal
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  2. Y van der Graaf
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  4. J Westerink
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Correspondence to F L J Visseren.

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The authors declare no conflict of interest.

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Koopal, C., van der Graaf, Y., Asselbergs, F. et al. Influence of APOE-2 genotype on the relation between adiposity and plasma lipid levels in patients with vascular disease. Int J Obes 39, 265–269 (2015). https://doi.org/10.1038/ijo.2014.105

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