Nonalcoholic fatty liver disease (NAFLD) is currently the most common chronic liver disease worldwide in part due to the concomitant obesity pandemic and insulin resistance (IR). It is increasingly becoming evident that NAFLD is a disease affecting numerous extrahepatic vital organs and regulatory pathways. The molecular mechanisms underlying the nonalcoholic steatosis formation are poorly understood, and little information is available on the pathways that are responsible for the progressive hepatocellular damage that follows lipid accumulation. Recently, much research has focused on the identification of the epigenetic modifications that contribute to NAFLD pathogenesis. Noncoding RNAs (ncRNAs) are one of such epigenetic factors that could be implicated in the NAFLD development and progression. In this review, we summarize the current knowledge of the genetic and epigenetic factors potentially underlying the disease. Particular emphasis will be put on the contribution of microRNAs (miRNAs), long noncoding RNAs (lncRNAs), and circular RNAs (circRNAs) to the pathophysiology of NAFLD as well as their potential use as therapeutic targets or as markers for the prediction and the progression of the disease.

Rheumatoid arthritis (RA) is an autoimmune disease that predominantly affects women. MicroRNAs have emerged as crucial regulators of the immune system, whose expression is deregulated in RA. We aimed at quantifying the expression level of 14 miRNAs located on the X chromosome and at identifying whether differences are associated with disease and/or sex. A case–control study of 21 RA patients and 22 age- and sex-matched healthy controls was performed on peripheral blood mononuclear cells. The expression level of five miRNAs (miR-221, miR-222, miR-532, miR-106a, and miR-98) was significantly different between RA and controls when stratifying by sex, and the expression level of four miRNAs (miR-222, miR-532, miR-98, and miR-92a) was significantly different between RA females and males. The expression quantitative trait loci (eQTL) analysis revealed a significant gender effect of the FoxP3 promoter polymorphism rs3761548A/C on miR-221, miR-222 and miR-532 expression levels, and of the FoxP3 polymorphism rs2232365A/G on miR-221 expression levels in PBMC of RA patients. These data further support the involvement of the X chromosome in RA susceptibility. X-linked miRNAs, in the context of sex differences, might provide novel insight into new molecular mechanisms and potential therapeutic targets in RA for disease treatment and prevention.