Project1. Plasma levels of 2083 miRNAs were measured by RNA sequencing in 1999 participants from the 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 and CT-based FLD. Moreover, the association of miRNAs with hepatic steatosis and liver fibrosis was assessed longitudinally in individuals who underwent abdominal ultrasound and transient elastography after a median follow-up of >6 years. We found 61 miRNAs significantly associated with serum GGT and ALP as well as 17 miRNAs associated with CT-based FLD, 14 of them were among the miRNAs associated with liver enzymes. Longitudinal analysis showed 4 (miR-193a-5p, miR-122-5p, miR-378d and miR-187-3p) of the 14 miRNAs significantly associated with hepatic steatosis and three (miR-193a-5p, miR-122-5p and miR-193b-3p) nominally associated with liver fibrosis.

Circulatory microRNAs as potential biomarkers for fatty liver disease: the Rotterdam study. Zhang X, …, Ghanbari M.
Aliment Pharmacol Ther. 2021 Feb;53(3):432-442. doi: 10.1111/apt.16177.

Project2. We describe briefly the potential clinical applications of microRNAs for the diagnosis of fatty liver disease.
 
Editorial: microRNAs for the diagnosis of fatty liver disease in the population-are we inching closer towards the target? Authors’ reply. Zhang X, Ghanbari M. Aliment Pharmacol Ther. 2021 Feb;53(4):559-560. doi: 10.1111/apt.16234.

Project3. We performed a systematic review of human epigenetic studies on FLD. In total 36 articles, based on 33 unique studies, consisting of 12,112 participants met the inclusion criteria. Among these, two recent epigenome-wide association studies conducted among large population-based cohorts have reported the association between cg06690548 (SLC7A11) and FLD. Moreover, several studies have demonstrated the association between miRNAs and FLD, in which miR-122, miR-34a and miR-192 were recognized as the most relevant miRNAs as biomarkers for FLD.

Deciphering the role of epigenetic modifications in fatty liver disease: A systematic review. Zhang X, …, Ghanbari M.
Eur J Clin Invest. 2021 May;51(5):e13479. doi: 10.1111/eci.13479.