NLRP13 inflammasome complex is hypermethylated in familial Mediterranean fever and global methylation correlates with the disease severity

Abstract

Familial Mediterranean fever (FMF) is an autoinflammatory disease caused by variations in the MEFV gene, which encodes the pyrin protein, a member of the inflammasomes. Despite the complex pathogenesis of FMF, epigenetic changes also play roles in the disease progression. In our previous study, we observed a relationship between NLRP13, which is one of the members of the inflammasome complex and has a pyrin domain in its structure, and the MEFV gene using the STRING database. In this study, we examined NLRP13 expression and methylation status in 40 patients with FMF attack and 20 healthy individuals. We then investigated the global DNA methylation status of patients with FMF in the attack period and control groups. We further examined the relationship between the clinical manifestation and global methylation as well as NLRP13 gene expression of patients with FMF and healthy individuals. As a result, we showed that hypomethylation in patients with FMF leads to different clinical outcomes in terms of disease severity. In addition, the data indicated that NLRP13 inflammasome is epigenetically controlled in patients with FMF and the presence of amyloidosis may affect the hypermethylation of this gene. Moreover, NLRP13 was silenced because of the hypermethylation of the promoter. The increase of methylation level at the promoter region participated in the inactivation of NLRP13. In the current study, we not only found a new gene that plays a role in the pathogenesis of FMF disease, but also new evidence for the epigenetic regulation of the disease.

Deciphering the prognostic significance and regulatory networks of ZEB1 and ZEB2 in prostate adenocarcinoma

“…The discrepancy between low expression of ZEB1 and ZEB2 in PRAD samples, as indicated by gene expression analyses, and their high expression as revealed by IHC. It has been reported that microRNAs such as miR-203, miR-200a, miR-525-5p, miR-127, miR-101-3p and miR-186-5p play a role in the EMT pathway by downregulated ZEB1 and ZEB2 in various cancers including gastric, breast, and colorectal [31,32]. Despite this, the intricacies of post-transcriptional regulation, involving factors like microRNAs and RNA stability, have the potential to influence protein synthesis.…”

Updates on the role of epigenetics in familial mediterranean fever (FMF)

“…In fact, the presence of amyloidosis was associated with hypermethylation of the NRLP13 gene, hence resulting in its silencing and subsequently in the inhibition of inflammasome assembly. This discovery unveiled a new epigenetic mechanism contributing to the development of FMF [ 40 ]. The NLRP3 inflammasome was also found to be significantly demethylated in monocytes derived from FMF patients and associated with increased expression of IL-1β [ 41 ].…”

Epigenetic, transcriptional, and functional characterization of myeloid cells in familial Mediterranean fever

“… 29 It has never been assessed if the IL-1-enrichment in FMF patients affects the epigenetic programming of monocytes specifically, although a recent study found that global DNA methylation is correlated with disease severity. 30 This indicates a more detailed epigenetic investigation is warranted in FMF.…”