Plasma ApoE elevations are associated with NAFLD: The PREVEND Study

Eline H van den Berg; James P Corsetti; Stephan J L Bakker; Robin P F Dullaart

doi:10.1371/journal.pone.0220659

Plasma ApoE elevations are associated with NAFLD: The PREVEND Study

PLoS One. 2019 Aug 6;14(8):e0220659. doi: 10.1371/journal.pone.0220659. eCollection 2019.

Authors

Eline H van den Berg^{1

2}, James P Corsetti³, Stephan J L Bakker⁴, Robin P F Dullaart¹

Affiliations

¹ Department of Endocrinology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
² Department of Gastroenterology and Hepatology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
³ Department of Pathology and Laboratory Medicine, University of Rochester School of Medicine and Dentistry, Rochester, New York, United States of America.
⁴ Department of Nephrology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.

Abstract

Non-alcoholic fatty liver disease (NAFLD) is featured by increased plasma very low density lipoproteins (VLDL). The extent to which plasma apolipoprotein E (ApoE) levels are elevated in NAFLD is unclear. We determined whether plasma ApoE is elevated in subjects with suspected NAFLD. Plasma ApoE and genotypes were determined in 6,762 participants of the Prevention of Renal and Vascular End-Stage Disease (PREVEND) cohort. A Fatty Liver Index (FLI) ≥ 60 was used as a proxy of NAFLD. A total of 1,834 participants had a FLI ≥ 60, which coincided with increased triglycerides, non-HDL cholesterol, ApoB and ApoE (all P<0.001). In multivariable linear regression analysis, plasma ApoE levels were positively associated with an elevated FLI when taking account of ApoE genotypes and other clinical and laboratory covariates (fully adjusted model: β = 0.201, P<0.001). Stratified analysis for ApoE genotypes (ApoE ε3ε3 homozygotes, ApoE ε2 carriers, and ApoE ε3ε4 and ε4ε4 carriers combined), also showed positive associations of plasma ApoE levels with an elevated FLI in each group (all P<0.001). In conclusion, it is suggested that NAFLD is characterized by increased plasma ApoE levels, even when taking account of the various ApoE genotypes. Increased plasma ApoE may contribute to altered VLDL metabolism and to increased atherosclerosis susceptibility in NAFLD.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adult
Aged
Apolipoproteins E / blood*
Atherosclerosis / etiology
Female
Genotype
Humans
Linear Models
Lipoproteins, VLDL / metabolism
Male
Middle Aged
Non-alcoholic Fatty Liver Disease / blood*
Non-alcoholic Fatty Liver Disease / complications

Substances

Apolipoproteins E
Lipoproteins, VLDL

Grants and funding

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 Dutch Heart Foundation supported studies on lipid metabolism (Grant 2001-005). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.