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代谢特征和细胞因子基因多态性作为非酒精性脂肪性肝病患者肝纤维化程度较高的潜在危险因素:一项基于医院的研究。

Metabolic Characteristics and Cytokine Gene Polymorphisms as Potential Risk Factors for a Higher Liver Fibrosis Stage in MASLD Patients: A Hospital-Based Study.

作者信息

Iancu Mihaela, Coste Sorina-Cezara, Cozma Angela, Orășan Olga Hilda, Lucaciu Roxana Liana, Hangan Adriana Corina, Para Ioana, Gog Bogdan Sidonia, Procopciuc Lucia-Maria

机构信息

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.

出版信息

Int J Mol Sci. 2025 Apr 15;26(8):3730. doi: 10.3390/ijms26083730.

Abstract

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.

摘要

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。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c7fc/12027573/7c18c18290cb/ijms-26-03730-g001.jpg

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