Open AccessTranscriptomic profiling of a multiethnic pediatric NAFLD cohort reveals genes and pathways associated with disease
Author(s) -
Yao Kangning,
Tarabra Elena,
Sia Daniela,
Morotti Raffaella,
Fawaz Rima,
Valentino Pamela,
Santoro Nicola,
Caprio Sonia,
Liu Silvia,
Yimlamai Dean
Publication year - 2022
Publication title -
hepatology communications
Language(s) - English
Resource type - Journals
ISSN - 2471-254X
DOI - 10.1002/hep4.1940
Subject(s) - nonalcoholic fatty liver disease , igfbp3 , transcriptome , liver biopsy , disease , gene signature , population , chronic liver disease , biology , bioinformatics , biomarker , medicine , liver disease , fatty liver , gene , biopsy , genetics , gene expression , growth factor , receptor , environmental health , cirrhosis
Nonalcoholic fatty liver disease (NAFLD) is the most common type of chronic liver disease in children. The mechanisms that drive NAFLD disease progression in this specific patient population remain poorly defined. In this study, we obtained liver biopsy samples from a multiethnic cohort of pediatric patients with NAFLD (n = 52, mean age = 13.6 years) and healthy liver controls (n = 5). We analyzed transcriptomic changes associated with NAFLD stages using high‐throughput RNA sequencing. Unsupervised clustering as well as pairwise transcriptome comparison distinguished NAFLD from healthy livers. We identified perturbations in pathways including calcium and insulin/glucose signaling occurring early in NAFLD disease, before the presence of histopathologic evidence of advanced disease. Transcriptomic comparisons identified a 25‐gene signature associated with the degree of liver fibrosis. We also identified expression of the insulin‐like growth factor binding protein (IGFBP) gene family (1/2/3/7) as correlating with disease stages, and it has the potential to be used as a peripheral biomarker in NAFLD. Comparing our data set with publicly available adult and adolescent transcriptomic data, we identified similarities and differences in pathway enrichment and gene‐expression profiles between adult and pediatric patients with NAFLD. Regulation of genes including interleukin‐32, IGFBP1, IGFBP2, and IGFBP7 was consistently found in both NAFLD populations, whereas IGFBP3 was specific to pediatric NAFLD. Conclusion: This paper expands our knowledge on the molecular mechanisms underlying pediatric NAFLD. It identifies potential biomarkers and directs us toward new therapies in this population.