Iancu Mihaela, Coste Sorina-Cezara, Cozma Angela, Orășan Olga Hilda, Lucaciu Roxana Liana, Hangan Adriana Corina, Para Ioana, Gog Bogdan Sidonia, Procopciuc Lucia-Maria
Medical Informatics and Biostatistics, Faculty of Nursing and Health Science, "Iuliu Hațieganu" University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania.
4th Department of Internal Medicine, Faculty of Medicine, "Iuliu Hațieganu" University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania.
Int J Mol Sci. 2025 Apr 15;26(8):3730. doi: 10.3390/ijms26083730.
Polymorphisms in the Toll-like receptor 4 (TLR4) and IL-17 cytokine genes play a role in liver fibrosis progression among patients with MASLD. The current study aimed to investigate whether the ( and ) and ( and ) gene polymorphisms are associated with increased liver fibrosis stages in MASLD patients. Genotyping for the -, -, -, and - polymorphisms was performed on a sample of 42 MASLD patients and 39 healthy controls. Serum levels of IL17F, IL17A, and TLR4 were measured using ELISA techniques. Bivariate analysis revealed significant associations between glycemic levels ( = 0.006), lipid metabolism (total cholesterol, HDL cholesterol, triglycerides), and the severity of liver fibrosis ( < 0.05). The - GA and AA genotypes were more frequent in patients with advanced liver fibrosis compared to those without fibrosis (GA genotype frequency: 42.9% vs. 7.7%; AA genotype frequency: 14.3% vs. 5.1%; adjusted = 0.0423). In the multivariable ordinal logistic regression, the - polymorphism remained significantly associated with higher liver fibrosis stages (adjusted = 0.0155). Patients with the dominant genotype (GA + AA) of the - polymorphism exhibited 3.91 times greater odds of experiencing at least a one-stage increase in liver fibrosis compared to those with the GG genotype (adjusted OR = 3.91, 95% CI: 1.33-12.34). This study indicates that -related genetic polymorphisms and metabolic characteristics significantly affect liver fibrosis progression in MASLD patients, with the - gene polymorphism identified as an independent multivariate predictor of fibrosis progression.
Toll样受体4（TLR4）和白细胞介素17（IL-17）细胞因子基因多态性在非酒精性脂肪性肝病（MASLD）患者的肝纤维化进展中起作用。本研究旨在调查TLR4（rs11536889和rs4986790）和IL-17（rs763780和rs2275913）基因多态性是否与MASLD患者肝纤维化分期增加相关。对42例MASLD患者和39例健康对照样本进行了rs11536889、rs4986790、rs763780和rs2275913多态性的基因分型。采用酶联免疫吸附测定（ELISA）技术检测血清IL17F、IL17A和TLR4水平。双变量分析显示血糖水平（P = 0.006）、脂质代谢（总胆固醇、高密度脂蛋白胆固醇、甘油三酯）与肝纤维化严重程度之间存在显著关联（P < 0.05）。与无肝纤维化患者相比，晚期肝纤维化患者中TLR4 - rs11536889的GA和AA基因型更为常见（GA基因型频率：42.9% 对7.7%；AA基因型频率：14.3% 对5.1%；校正P = 0.0423）。在多变量有序逻辑回归中，TLR4 - rs11536889多态性仍与较高的肝纤维化分期显著相关（校正P = 0.0155）。与GG基因型患者相比，TLR4 - rs11536889多态性显性基因型（GA + AA）的患者肝纤维化至少增加一期的几率高3.91倍（校正OR = 3.91，95%置信区间：1.33 - 12.34）。本研究表明，TLR4相关基因多态性和代谢特征显著影响MASLD患者的肝纤维化进展，TLR4基因多态性被确定为纤维化进展的独立多变量预测因子。
