Adiposity and the development of dyslipidemia in APOE ε2 homozygous subjects: A longitudinal analysis in two population-based cohorts

Britt E. Heidemann, Frank J. Wolters, Maryam Kavousi, Eke G. Gruppen, Robin PF Dullaart, A. David Marais, Frank LJ Visseren*, Charlotte Koopal

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

8 Citations (Scopus)
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Background and aims: Familial dysbetalipoproteinemia (FD), characterized by remnant lipoprotein accumulation and premature cardiovascular disease, occurs in homozygous carriers of the APOE ε2 allele, but genetic predisposition alone does not suffice for the clinical phenotype. Cross-sectional studies suggest that a second metabolic hit – notably adiposity or insulin resistance – is required, but the association between these risk factors and development of FD has not been studied prospectively. Methods: For this study, we evaluated 18,987 subjects from two large prospective Dutch population-based cohorts (PREVEND and Rotterdam Study) of whom 118 were homozygous APOE ε2 carriers. Of these, 69 subjects were available for prospective analyses. Dyslipidemia – likely to be FD – was defined as fasting triglyceride (TG) levels >3 mmol/L in untreated subjects or use of lipid lowering medication. The effect of weight, body mass index (BMI), waist circumference, type 2 diabetes mellitus and non-TG metabolic syndrome on development of dyslipidemia was investigated. Results: Eleven of the 69 ε2ε2 subjects (16%) developed dyslipidemia – likely FD – during follow-up. Age-, sex- and cohort-adjusted risk factors for the development of FD were BMI (OR 1.19; 95%CI 1.04–1.39), waist circumference (OR 1.26 95%CI 1.01–1.61) and presence of non-TG metabolic syndrome (OR 4.39; 95%CI 1.04–18.4) at baseline. Change in adiposity during follow-up was not associated with development of dyslipidemia. Conclusions: Adiposity increases the risk of developing an FD-like lipid phenotype in homozygous APOE ε2 subjects. These results stress the importance of healthy body weight in subjects at risk of developing FD.

Original languageEnglish
Pages (from-to)57-62
Number of pages6
Early online date20 Apr 2021
Publication statusPublished - May 2021

Bibliographical note

Funding Information:
The Dutch Kidney Foundation supported the infrastructure of the PREVEND program from 1997 to 2003 (Grant E.033). The University Medical Center Groningen supported the infrastructure from 2003 to 2006. Dade Behring, Ausam, Roche, and Abbott financed laboratory equipment and reagents by which various laboratory determinations could be performed. The Rotterdam Study is supported by the Erasmus Medical Center and Erasmus University Rotterdam, The Netherlands Organization for Scientific Research (NWO), The Netherlands Organization for Health Research and Development (ZonMW), the Research Institute for Diseases in the Elderly (RIDE), The Netherlands Genomics Initiative, the Ministry of Education, Culture and Science, the Ministry of Health, Welfare and Sports, the European Commission (DG XII), and the Municipality of Rotterdam.

Publisher Copyright:
© 2021 The Authors


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