Department of Epidemiology, Erasmus University Medical Center, Rotterdam, the Netherlands.
Department of Radiology and Nuclear Medicine, Erasmus University Medical Center, Rotterdam, the Netherlands.
Aliment Pharmacol Ther. 2021 Feb;53(3):432-442. doi: 10.1111/apt.16177. Epub 2020 Nov 27.
Fatty liver disease (FLD) is the most common cause of liver dysfunction in developed countries. There is great interest in developing clinically valid and minimally invasive biomarkers to enhance early diagnosis of FLD.
To investigate the potential of circulatory microRNAs (miRNAs) as biomarkers of FLD at the population level.
Plasma levels of 2083 miRNAs were measured by RNA sequencing in 1999 participants from the prospective population-based Rotterdam Study cohort. The Hounsfield Unit (HU) attenuation of liver was measured using non-enhanced computed tomography (CT) scan. Logistic and linear regression models adjusting for potential confounders were used to examine the association of circulatory miRNAs with liver enzymes (n = 1991) and CT-based FLD (n = 954). Moreover, the association of miRNAs with hepatic steatosis and liver fibrosis was assessed longitudinally in individuals who underwent abdominal ultrasound (n = 1211) and transient elastography (n = 777) after a median follow-up of >6 years.
Cross-sectional analysis showed 61 miRNAs significantly associated with serum gamma-glutamyl transferase and/or alkaline phosphatase levels (Bonferroni-corrected P < 8.46 × 10 ). Moreover, 17 miRNAs were significantly associated with CT-based FLD (P < 8.46 × 10 ); 14 were among miRNAs associated with liver enzymes. Longitudinal analysis showed that 4 of these 14 miRNAs (miR-193a-5p, miR-122-5p, miR-378d and miR-187-3p) were significantly associated with hepatic steatosis (P < 3.57 × 10 ) and three (miR-193a-5p, miR-122-5p and miR-193b-3p) were nominally associated with liver fibrosis (P < 0.05). Nine of the 14 identified miRNAs were involved in pathways underlying liver diseases.
Plasma levels of several miRNAs can be used as biomarkers of FLD, laying the groundwork for future clinical applications.
脂肪肝疾病（FLD）是发达国家最常见的肝功能失调原因。人们非常希望开发出临床有效和微创的生物标志物，以增强对 FLD 的早期诊断。
在人群水平上研究循环 microRNAs（miRNAs）作为 FLD 生物标志物的潜力。
通过 RNA 测序测量了来自前瞻性人群为基础的鹿特丹研究队列的 1999 名参与者的血浆中 2083 种 miRNAs 的水平。使用非增强型计算机断层扫描（CT）扫描测量肝脏的 Hounsfield 单位（HU）衰减。使用调整了潜在混杂因素的逻辑和线性回归模型，研究了循环 miRNA 与肝酶（n=1991）和基于 CT 的 FLD（n=954）之间的关联。此外，在中位随访时间超过 6 年后，对接受腹部超声（n=1211）和瞬时弹性成像（n=777）检查的个体进行了 miRNA 与肝脂肪变性和肝纤维化的纵向关联评估。
横断面分析显示，61 种 miRNA 与血清 γ-谷氨酰转移酶和/或碱性磷酸酶水平显著相关（Bonferroni 校正 P<8.46×10）。此外，17 种 miRNA 与基于 CT 的 FLD 显著相关（P<8.46×10）；其中 14 种 miRNA 与肝酶相关。纵向分析显示，这 14 种 miRNA 中的 4 种（miR-193a-5p、miR-122-5p、miR-378d 和 miR-187-3p）与肝脂肪变性显著相关（P<3.57×10），3 种（miR-193a-5p、miR-122-5p 和 miR-193b-3p）与肝纤维化呈名义相关（P<0.05）。在鉴定的 14 种 miRNA 中有 9 种参与了肝脏疾病的相关途径。
血浆中几种 miRNAs 的水平可用作 FLD 的生物标志物，为未来的临床应用奠定了基础。
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