Published online Jan 28, 2022. doi: 10.3748/wjg.v28.i4.449
Peer-review started: April 18, 2021
First decision: June 3, 2021
Revised: June 16, 2021
Accepted: January 11, 2022
Article in press: January 11, 2022
Published online: January 28, 2022
Processing time: 278 Days and 22.6 Hours
Celiac disease (CeD) is a multifactorial autoimmune disorder spread worldwide. The exposure to gluten, a protein found in cereals like wheat, barley and rye, is the main environmental factor involved in its pathogenesis. Even if the genetic predisposition represented by HLA-DQ2 or HLA-DQ8 haplotypes is widely recognised as mandatory for CeD development, it is not enough to explain the total predisposition for the disease. Furthermore, the onset of CeD comprehend a wide spectrum of symptoms, that often leads to a delay in CeD diagnosis. To overcome this deficiency and help detecting people with increased risk for CeD, also clarifying CeD traits linked to disease familiarity, different studies have tried to make light on other predisposing elements. These were in many cases genetic variants shared with other autoimmune diseases. Since inherited traits can be regulated by epigenetic modifications, also induced by environmental factors, the most recent studies focused on the potential involvement of epigenetics in CeD. Epigenetic factors can in fact modulate gene expression with many mechanisms, generating more or less stable changes in gene expression without affecting the DNA sequence. Here we analyze the different epigenetic modifications in CeD, in particular DNA methylation, histone modifications, non-coding RNAs and RNA methylation. Special attention is dedicated to the additional predispositions to CeD, the involvement of epigenetics in developing CeD complications, the pathogenic pathways modulated by epigenetic factors such as microRNAs and the potential use of epigenetic profiling as biomarker to discriminate different classes of patients.
Core Tip: Currently identified genes account only for half of celiac disease (CeD) predisposition. An important role could be played by epigenetics, inheritable traits without DNA sequence alterations, which could be influenced by gluten exposure. DNA methylation, histone modifications and non-coding RNAs act on different gene expression steps, from gene transcription to post-translational ones. Epigenetic changes can be additional predisposition factors or specific of CeD stages (active disease, gluten-free diet) as recently reported. Analysis of epigenetic data and their integration with transcriptome (by machine learning) can help to stratify patients, or discover new players in CeD pathogenesis, possible focus of novel therapeutic approaches.