Plasma proteomic signature of fatty liver disease: The Rotterdam Study.

Autor:	Abozaid YJ; Department of Epidemiology, Erasmus MC University Medical Center, Rotterdam, The Netherlands., Ayada I; Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center, Rotterdam, The Netherlands., van Kleef LA; Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center, Rotterdam, The Netherlands., Vallerga CL; Department of Internal Medicine, Erasmus MC University Medical Center, Rotterdam, The Netherlands., Pan Q; Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center, Rotterdam, The Netherlands., Brouwer WP; Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center, Rotterdam, The Netherlands., Ikram MA; Department of Epidemiology, Erasmus MC University Medical Center, Rotterdam, The Netherlands., Van Meurs J; Department of Internal Medicine, Erasmus MC University Medical Center, Rotterdam, The Netherlands.; Department of Orthopaedics and Sportsmedicine, Erasmus MC University Medical Center, Rotterdam, The Netherlands., de Knegt RJ; Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center, Rotterdam, The Netherlands., Ghanbari M; Department of Epidemiology, Erasmus MC University Medical Center, Rotterdam, The Netherlands.
Jazyk:	angličtina
Zdroj:	Hepatology (Baltimore, Md.) [Hepatology] 2023 Jul 01; Vol. 78 (1), pp. 284-294. Date of Electronic Publication: 2023 Feb 06.
DOI:	10.1097/HEP.0000000000000300
Abstrakt:	Background and Aims: Fatty liver disease (FLD) is caused by excess fat in the liver, and its global prevalence exceeds 33%. The role of protein expression on the pathogenesis of FLD and accompanied fibrosis and its potential as a disease biomarker is currently not clear. Hence, we aimed to identify plasma proteomics associated with FLD and fibrosis using population-based data. Approach and Results: Blood samples were collected from 2578 participants from the population-based Rotterdam Study cohort. The proximity extension assay reliably measured plasma levels of 171 cardiometabolic and inflammatory-related proteins (Olink Proteomics). FLD was assessed by ultrasound, and fibrosis by transient elastography. Logistic regression models quantified the association of plasma proteomics with FLD and fibrosis. In addition, we aimed to validate our results in liver organoids. The cross-sectional analysis identified 27 proteins significantly associated with FLD surpassing the Bonferroni-corrected p <2.92×10 -4 . The strongest association was observed for FGF-21 (β=0.45, p =1.07×10 -18 ) and carboxylesterase 1 (CES1) protein (β=0.66, p =4.91×10 -40 ). Importantly, 15 of the 27 proteins significantly associated with FLD were also associated with liver fibrosis. Finally, consistent with plasma proteomic profiling, we found the expression levels of IL-18 receptor 1 (IL-18R1) and CES1 to be upregulated in an FLD model of 3-dimensional culture human liver organoids. Conclusions: Among the general population, several inflammatory and cardiometabolic plasma proteins were associated with FLD and fibrosis. Particularly, plasma levels of FGF-21, IL-18R1, and CES1 were largely dependent on the presence of FLD and fibrosis and may therefore be important in their pathogenesis. (Copyright © 2023 American Association for the Study of Liver Diseases.)
Databáze:	MEDLINE
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