Cholesteryl Ester Transfer Protein Variant (RS1800777) with Liver Histology in Non-Alcoholic Fatty Liver Disease Patients

Abstract

Introduction and Aims: Non-alcoholic fatty liver disease (NAFLD) is a spectrum of diseases ranging from simple steatosis without inflammation or fibrosis to nonalcoholic steatohepatitis and in the Western countries has become one of the most prevalent chronic liver diseases related to metabolic and lipid alterations. Cholesteryl ester transfer protein (CETP) participates in high density lipoprotein (HDL)-cholesterol metabolism. The aim of our study was to investigate the influence of polymorphism (rs1800777) of CETP gene on liver histological changes, biochemical parameters, and serum adipokines levels in patients with NAFLD. Material and Methods: A population of 90 patients with NAFLD was recruited in a cross-sectional study. A biochemical analysis (glucose, c-reactive protein, insulin, homeostasis model assessment-insulin resistance, total cholesterol, low density lipoprotein (LDL)-cholesterol, HDL-cholesterol, triglycerides blood, and adipokines (leptin, adiponectin, and resistin) was realized. Genotype of polymorphism (rs1800777) of CETP gene was studied. Results: Eighty-three patients (92.2%) had the genotype GG (wild type group) and 7 patients (7.8%) had the genotype GA (n = 7) or AA (n = 0; mutant type group). Patients with A allele show significant decrease in liver biochemistry parameters – Alanine amino transferase (delta 10.1 ± 9.9 UI/L; p = 0.01), aspartate aminotransferase activity (delta 13.3 ± 9.5 UI/L; p = 0.02), and gammaglutamine transferase levels (delta 39 ± 30.1 UI/L; p = 0.01). Logistic regression analysis indicated that subjects with A-allele carriers were associated with a decreased risk of lobulillar inflammation (OR 0.18, 95% CI 0.04–0.95, p = 0.04) and a decreased risk of steatosis (OR 0.13, 95% CI 0.02–0.89, p = 0.04). Conclusions: A variant of the polymorphism rs1800777 of CETP gene is independently associated with the presence of steatosis and lobulillar inflammation in subjects with proven biopsy NAFLD.

Pathophysiological, Molecular and Therapeutic Issues of Nonalcoholic Fatty Liver Disease: An Overview

“…It is primarily derived from Kupffer cells [137]. The variant rs1800777 of this gene has recently been associated with liver steatosis and lobular inflammation in patients with biopsy proven NAFLD [138].…”

Both full length‐cholesteryl ester transfer protein and exon 9‐deleted cholesteryl ester transfer protein promote triacylglycerol storage in cultured hepatocytes

“…Unlike adipocytes, in hepatocytes overexpressing either FL‐CETP and ∆E9‐CETP, or Caco‐2 cells overexpressing FL‐CETP, CETP promotes the accumulation of cellular TAG. These findings provide a possible mechanism for the direct association between CETP expression and hepatic steatosis observed in human studies (Adams et al, 2012; Aller et al, 2018; Fadaei et al, 2018; Lucero et al, 2011; Yoo et al, 2019).…”

Aktualisierte S2k-Leitlinie nicht-alkoholische Fettlebererkrankung der Deutschen Gesellschaft für Gastroenterologie, Verdauungs- und Stoffwechselkrankheiten (DGVS) – April 2022 – AWMF-Registernummer: 021–025

“…Die Ergebnisse sieben interventioneller 279 321 322 323 324 325 326 und vier Beobachtungs-Studien 327 328 329 330 legen nahe, dass eine mediterrane Ernährung (ME) günstige Auswirkungen auf Körpergewicht und Insulinsensitivität sowie hepatische Steatose hat. Zur präventiven Wirksamkeit der ME bezüglich des Auftretens einer NAFLD ist die Datenlage jedoch weniger klar 117 282 331 332 .…”