Epigenetic changes in celiac disease

Fatemeh Khajooee,1,* Fatemeh hendijani,2

1. Student Research Committee, Faculty of Pharmacy, Hormozgan University of Medical Sciences, Bandar Abbas, Iran
2. Department of Pharmacognosy and Pharmaceutical Biotechnology, Faculty of Pharmacy, Hormozgan University of Medical Sciences, Bandar Abbas, Iran

Abstract

Introduction

Celiac disease (cd) is a gluten-sensitive enteropathy mediated by the immune system and considered one of the most complex genetic diseases. genetic and epigenetic factor were known to play role in pathology of the disease (fernandez-jimenez). the rate of concordance in monozygotic twins is about 75 %, it is suggested that approximately 60–90% of the variance in liability to the disease had a genetic origin, while environmental factors correspond for 10-40% of disease liability. heritability implies that an epigenetic marker has the ability to persist during development and that is potentially transmitted from generation to generation epigenetic programming, including cpg methylation and histone modifications, and non-coding rna functios occurring during early postnatal development can influence the risk of disease in later life. dna methylation is carried out by a class of enzymes called dna methyltransferases dnmts, which depend on the levels of sadenosylmethionine (sam). sam acts a methyl donor for over 200 methylation levels and is converted to s- denosylhomocysteine (sah), an inhibitor of methylation reactions. in this review we were going to review all studies in which epigenetic changes were investigated in celiac disease.

Methods

In order to find related studies in the literature, pubmed and scopus databases was searched. following key terms was applied:("non coding rnas" and "celiac disease") and ("dna methylation" and "celiac disease") and ("histone modification" and "celiac disease") . no limitation for language and year of publication was applied in the search. all studies in which epigenetic changes in celiac disease were entered for data extraction.

Results

21 related studies were found after database search. all full texts were screened for data extraction. dna methylation at 8 nfkb-related genes and non-coding rnas were found to affect celiac disease. nfkb is a major mediator of il15, which is able to decrease claudin-2 levels in epithelial tight junction structures and leads to augmented paracellular permeability, on the other hand genetic polymorphisms in key nfkb-mediators such as rel and tnfaip3 have been associated with susceptibility to cd. other studies also showed that of the 22 genes that are constitutively overexpressed in cd mucosa, 7 (ikbkb, ikbkg, irak1, map3k14, nfkb2, nfkbie and traf2) are core proteins coding genes. another three genes are members of the mapk family, which has been demonstrated central to the nfkb system by direct interaction, uniprot annotation and manual curation approaches. the association of cd with genes that affect 3’ utr sequences could lead to a decreased stability or increased degradation of the respective mrna. on the other hand, they could promote the inhibition of protein translation by altering binding sites of rnas or affect binding sites to mirnas.

Conclusion

Dna methylation at nfkb-related genes and map kinase family and also function of non-coding rnas can affect pathology of celiac disease and control of immuneresponse. these results could humbly help configuring a novel point of view, to elucidate how epigenetic alterations participate in the development and course of cd and also how their modification help to find new effective treatments.

Keywords

Non coding rnas , celiac disease , dna methylation , histone modification , epigenetics