The clinical and pathogenetic role of lncRNA MEG3 and miRNA-421 in obese children with non-alcoholic fatty liver disease

Abstract

The danger of a “silent epidemic” of non-alcoholic fatty liver disease (NAFLD) in children is the growing number of patients with irreversible liver disease, comorbid conditions, high rate of disease progression compared to adults, so finding biomarkers of early stages of NAFLD is crucial for effective treatment. Aim. To examine the differences in the circulating lncRNA MEG3 and miR-421 levels in children with NAFLD and obesity compared to normal weight and obese children without NAFLD and to study the relationship of transcriptome markers with clinical, laboratory and instrumental parameters. Materials and methods. 66 patients aged 8 to 17 years were included in the study. The mean age of patients was 12.40 ± 2.46 years. The presence of hepatic steatosis was determined by measuring the controlled attenuation parameter (CAP) with FibroScan®502 touch (Echosens, France). Based on the presence of hepatic steatosis (according to CAP) and obesity (according to body mass index), patients were divided into 3 groups: group 1 consisted of 29 obese patients with NAFLD, group 2 – 30 obese patients without hepatic steatosis, group 3 – 7 patients with normal weight without hepatic steatosis. Parameters of transaminase activity, carbohydrate metabolism and lipid metabolism were quantified, cytokeratin-18, cytokine profile were measured by enzyme-linked immunosorbent assay. Levels of circulating miR-421, lncRNA MEG3 were assessed by quantitative real-time polymerase chain reaction. Results. Comparative analysis of serum lncRNA MEG3 and miR-421 levels showed a significant increase in lncRNA MEG3 and miR-421 levels in obese children compared with those in the control group (P ˂ 0.05), as well as in patients with NAFLD compared with children in group 2 (P ˂ 0.05). Serum lncRNA MEG3 and miR-421 levels were moderately positively correlated with adipose tissue distribution parameters, the degree of obesity, the liver parenchyma elasticity, the degree of pancreatic steatosis. miR-421 was positively correlated with TNFα levels, the ratio of pro-inflammatory and anti-inflammatory cytokines, negatively – with HDL levels. The serum levels of lncRNA MEG3 and miR-421 showed a tendency for a positive correlation with HOMA-IR. Conclusions. In obese children with NAFLD, a significant increase in serum lncRNA MEG3 and miR-421 levels is observed, which is associated with excessive adipose tissue and its distribution parameters, the degree of liver and pancreatic steatosis, insulin resistance, inflammation, dyslipidemia, that may be useful for early diagnosis of NAFLD in pediatric clinical practice.