Plasma ApoE elevations are associated with NAFLD: The PREVEND Study.

Eline H Van Den Berg,Robin P F Dullaart,Stephan J L Bakker,James P Corsetti,Petter Bjornstad

doi:10.1371/journal.pone.0220659

Eline H Van Den Berg, Robin P F Dullaart + Show 3 more

Open Access

https://doi.org/10.1371/journal.pone.0220659

Copy DOI

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.

Highlights

Non-alcoholic fatty liver disease (NAFLD) is characterized by hepatic steatosis in the absence of alcohol abuse, and is emerging as the most common cause of chronic liver disease
Data are given in number with percentages (%), mean ± standard deviation (SD) for normally distributed data or median with interquartile ranges (IQR) for nonnormally distributed data
Body mass index (BMI), waist circumference, the waist/hip ratio, systolic and diastolic blood pressure, plasma glucose, hsCRP, ALT, AST, GGT, Urinary albumin excretion (UAE), total cholesterol, non-high density lipoprotein (HDL) cholesterol, LDL cholesterol and triglycerides were higher in subjects with an elevated Fatty Liver Index (FLI), but Estimated glomerular filtration rate (eGFR) and HDL cholesterol were lower in subjects with an elevated FLI (Table 1)

Summary

Introduction

Non-alcoholic fatty liver disease (NAFLD) is characterized by hepatic steatosis in the absence of alcohol abuse, and is emerging as the most common cause of chronic liver disease. The spectrum of NAFLD ranges from simple steatosis to non-alcoholic steatohepatitis (NASH), fibrosis and eventually cirrhosis [1,2,3]. NAFLD is considered to be the liver manifestation of the metabolic syndrome (MetS) and coincides with an increased risk for the development of type 2 diabetes mellitus (T2D) [1,3,4,5]. ApoE elevations in NAFLD metabolism (Grant 2001-005). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Methods

Results

Conclusion