Differential Associations of Circulating MicroRNAs With Pathogenic Factors in NAFLD. Issue 5 (13th March 2020)

• Record Type: Journal Article
• Authors: Ezaz, Ghideon; Trivedi, Hirsh D.; Connelly, Margery A.; Filozof, Claudia; Howard, Kellie; L.Parrish, Mark; Kim, Misung; Herman, Mark A.; Nasser, Imad; Afdhal, Nezam H.; Jiang, Z. Gordon; Lai, Michelle
• Is Part Of: Hepatology communications. Volume 4:Issue 5(2020)
• Page Start: 670
• Page End: 680
• Publication Date: 2020-03-13
• Subjects: Hepatology -- Periodicals; Liver -- Diseases -- Periodicals; Liver Diseases; Gastroenterology; Periodicals; Fulltext; Internet Resources; Periodicals; 616.36
• DOI: 10.1002/hep4.1501
• Languages: English
• ISSNs: 2471-254X

Abstract

Abstract : Nonalcoholic fatty liver disease (NAFLD) is a heterogeneous disease driven by genetic and environmental factors. MicroRNAs (miRNAs) serve as pleiotropic post‐transcriptional regulators of cellular pathways. Although several miRNAs have been associated with NAFLD and fibrosis, there are limited studies in humans examining their differential association with pathogenic factors or histological features of NAFLD. We examined the differential relationships of five of the best‐described circulating microRNAs (miR‐34a, miR‐122, miR‐191, miR‐192, and miR‐200a) with histological features and pathogenic factors of NAFLD. A cross‐sectional study was conducted to examine the relationship between relative levels of circulating microRNAs standardized by z ‐scores and histological features of NAFLD, common NAFLD genetic polymorphisms, and insulin resistance measured by the enhanced lipoprotein insulin resistance index in 132 subjects with biopsy‐proven NAFLD. We found that miR‐34a, miR‐122, miR‐192, miR‐200a, but not miR‐191, strongly correlate with fibrosis in NAFLD by increases of 0.20 to 0.40 SD ( P < 0.005) with each stage of fibrosis. In multivariate analysis, miR‐34a, miR‐122, and miR‐192 levels are independently associated with hepatic steatosis and fibrosis, but not lobular inflammation or ballooning degeneration, whereas miR‐200a is only associated with fibrosis. Among the four miRNAs, miR‐34a, miR‐122, and miR‐192 are associated with pathogenic factors of NAFLD, including insulin resistance measured by eLP‐IR, patatin‐like phospholipase domain containing 3 I148M, and transmembrane 6 superfamily 2 (TM6SF2) E167K polymorphisms. In contrast, miR‐200a is only associated with the TM6SF2 E167K variant. Finally, miR‐34a has the strongest predictive value for various stages of fibrosis, with C‐statistic approximates–combined predictive score for miRNAs. Conclusion: miR‐34a, miR‐122, miR‐192, and miR‐200a demonstrate strong associations with NAFLD severity by histology, but differential associations with pathogenic factors. Abstract : Although some micro RNAs have been associated with nonalcoholic liver disease, human studies are limited. We provide independent validation of four of the best described miRNA (34a, 122, 192, and 200a) in their association with NAFLD phenotype and fibrosis. We also examine differential association with pathogenesis (insulin resistance and genetics) of the four miRNA.