Related Experiment Video
Updated: May 3, 2026

Generation of a Rat Model of Acute Liver Failure by Combining 70% Partial Hepatectomy and Acetaminophen
Published on: November 27, 2019
TLR4 gene polymorphism in patients with nonalcoholic fatty liver disease in comparison to healthy controls
Safak Kiziltas1, Pinar Ata, Yasar Colak
11 Department of Gastroenterology, Goztepe Training and Research Hospital , Istanbul, Turkey .
Objectives:
Recent studies have suggested that bacterial overgrowth and endotoxemia along with its receptor, Toll-like receptor 4 (TLR-4), play a role in the pathogenesis of nonalcoholic fatty liver disease (NAFLD). The present study was designed to test and evaluate the TLR4 gene polymorphism in patients with NAFLD in comparison to healthy controls.
Methods:
A total of 119 patients [mean (standard deviation, SD) age 43.4 (11.5) years, 55.5% were males] with NAFLD and 80 healthy controls [mean (SD) age 40.9 (8.1) years, 67.5% were females)] were evaluated in terms of patient demographics, anthropometrics, blood biochemistry, liver histology, and ultrasonographic (USG) findings. Histological evaluation was performed in 111 patients, and blood samples were collected from 119 patients with NAFLD and 80 healthy persons. Allelic variants of TLR4 (Asp299Gly and Thr399Ile) were assayed by real-time PCR. Genomic DNA was amplified using FAM/VIC primers specific for allelic variants of TLR4 Asp299Gly and Thr399Ile with real-time PCR. Amplicons were analyzed with high-resolution melting on a Light Cycler 480 for detecting different melting patterns of polymorphic and wild-type alleles.
Results:
The number of the subjects with heterozygous mutation at genotype 299 (Asp299Gly) was significantly lower in the NAFLD than in the control group (23.8 vs. 10.9%, P=0.027). Logistic regression analysis revealed that female gender [odds ratio (OR)=2.984, 95% confidence interval (CI) 1.561-5.360, P=0.001] and heterozygous (Asp299Gly) mutation at codon 299 (OR=2.998, 95% CI 1.325-6.783, P=0.008) were the significant predictors of higher likelihood of TRL4 gene polymorphism-related prevention of NAFLD.
Conclusions:
As the first-time-in-humans controlled study related to investigation of TLR4 gene polymorphism in NAFLD, our findings contribute to the available data that TLR-4 signaling is pivotal for the pathogenesis of NASH and indicate that the TLR4 codon 299 heterozygous gene mutation (Asp299Gly) in humans may have a preventive role against the genesis of NAFLD.
Related Concept Videos
Pharmacogenetics of Drug Targets: β₂-Adrenergic Receptors, Apo E, Thymidylate Synthase
Effect of Hepatic Disease on Pharmacokinetics: Pathophysiologic Assessment and Liver Function Test
Pharmacogenomics: Identification of New Drug Targets
Effect of Hepatic Disease on Pharmacokinetics: Drug Dosing and Hepatic Blood Flow
Pharmacogenetic Phenotypes: Alterations in Pharmacokinetics, Drug Targets and Biologic Milieu

