Li Yan, Dai Changyong, Yang Haiqing, Zeng Huang, Ruan Yuhua, Dai Mingjia, Hao Jungui, Wang Liping, Yan Xuebing, Ji Fang
Graduate School, Xuzhou Medical University, Xuzhou, Jiangsu, China.
Central Laboratory, Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, China.
J Gastroenterol Hepatol. 2024 Dec;39(12):2872-2879. doi: 10.1111/jgh.16687. Epub 2024 Aug 1.
Fibroblast growth factor 19 (FGF19) is an intestinal-derived factor that plays a role in metabolic diseases. We performed a differential study of circulating FGF19 levels and investigated the causal effects of FGF19 on metabolic diseases using Mendelian randomization (MR).
Firstly, 958 subjects were included in the physical examination center of affiliated hospital from January 2019 to January 2021. Dividing the subjects into different subgroups to compare FGF19 levels. We conducted a two-sample MR analysis of genetically predicted circulating FGF19 in relation to alcohol, cardiovascular and metabolic biomarkers and diseases, and liver function biomarkers using publicly available genome-wide association study summary statistics data.
The circulating FGF19 levels in nonalcoholic fatty liver disease (NAFLD) patients were lower than those without NAFLD (P < 0.001). The FGF19 levels in participants with obese were lower than those without obese (P < 0.001). In two-sample MR analyses, genetically predicted higher circulating FGF19 levels was significantly associated with lower aspartate aminotransferase, γ-glutamyltransferase, triglycerides, total cholesterol, low-density lipoprotein, and C-reactive protein concentrations (P < 0.05) and a negative correlation with cardiovascular disease and cirrhosis whereas a positive association with type 2 diabetes mellitus (P < 0.05).
Our study found that circulating FGF19 levels were lower in NAFLD and obese populations. Additionally, our MR research results support the causal effects of FGF19 on improved liver function, lipids, and reduced the occurrence of inflammation, cardiovascular disease, and cirrhosis. We found a positive correlation with diabetes, which may indicate a compensatory increase in regulating above FGF19 resistance states in humans.
成纤维细胞生长因子19（FGF19）是一种肠道衍生因子，在代谢性疾病中发挥作用。我们进行了循环FGF19水平的差异研究，并使用孟德尔随机化（MR）方法研究了FGF19对代谢性疾病的因果效应。
首先，选取2019年1月至2021年1月在附属医院体检中心的958名受试者。将受试者分为不同亚组以比较FGF19水平。我们使用公开可用的全基因组关联研究汇总统计数据，对基因预测的循环FGF19与酒精、心血管和代谢生物标志物及疾病以及肝功能生物标志物进行了两样本MR分析。
非酒精性脂肪性肝病（NAFLD）患者的循环FGF19水平低于无NAFLD的患者（P < 0.001）。肥胖参与者的FGF19水平低于非肥胖者（P < 0.001）。在两样本MR分析中，基因预测的较高循环FGF19水平与较低的天冬氨酸转氨酶、γ-谷氨酰转移酶、甘油三酯、总胆固醇、低密度脂蛋白和C反应蛋白浓度显著相关（P < 0.05），与心血管疾病和肝硬化呈负相关，而与2型糖尿病呈正相关（P < 0.05）。
我们的研究发现，NAFLD和肥胖人群的循环FGF19水平较低。此外，我们的MR研究结果支持FGF19对改善肝功能、血脂以及减少炎症、心血管疾病和肝硬化发生的因果效应。我们发现其与糖尿病呈正相关，这可能表明在人类中调节上述FGF19抵抗状态存在代偿性增加。
