Department of Endocrinology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
Department of Gastroenterology and Hepatology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
PLoS One. 2019 Aug 6;14(8):e0220659. doi: 10.1371/journal.pone.0220659. eCollection 2019.
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.
非酒精性脂肪性肝病（NAFLD）的特征是血浆极低密度脂蛋白（VLDL）增加。NAFLD 患者血浆载脂蛋白 E（ApoE）水平升高的程度尚不清楚。我们旨在确定疑似 NAFLD 患者的血浆 ApoE 是否升高。在预防肾脏和血管终末期疾病（PREVEND）队列的 6762 名参与者中，确定了血浆 ApoE 和基因型。脂肪性肝病指数（FLI）≥60 用作 NAFLD 的替代指标。共有 1834 名参与者的 FLI≥60，这与甘油三酯、非高密度脂蛋白胆固醇、ApoB 和 ApoE 升高一致（均 P<0.001）。在多变量线性回归分析中，当考虑 ApoE 基因型和其他临床及实验室协变量时，血浆 ApoE 水平与升高的 FLI 呈正相关（完全调整模型：β=0.201，P<0.001）。对 ApoE 基因型（ApoE ε3ε3 纯合子、ApoE ε2 携带者和 ApoE ε3ε4 和 ε4ε4 携带者合并）进行分层分析，也显示了血浆 ApoE 水平与每个组中升高的 FLI 之间的正相关关系（均 P<0.001）。总之，提示 NAFLD 的特征是血浆 ApoE 水平升高，即使考虑到各种 ApoE 基因型也是如此。增加的血浆 ApoE 可能导致 VLDL 代谢改变，并增加 NAFLD 中的动脉粥样硬化易感性。
