Identification of Epigenetic Methylation Signatures With Clinical Value in Crohn's Disease.

Autor:	Moret-Tatay I; Inflammatory Bowel Disease Research Group, Health Research Institute La Fe (IIS La Fe), Valencia, Spain., Cerrillo E; Inflammatory Bowel Disease Research Group, Health Research Institute La Fe (IIS La Fe), Valencia, Spain.; Department of Gastroenterology, Hospital La Fe, Valencia, Spain., Sáez-González E; Inflammatory Bowel Disease Research Group, Health Research Institute La Fe (IIS La Fe), Valencia, Spain.; Department of Gastroenterology, Hospital La Fe, Valencia, Spain., Hervás D; Biostatistics Unit, Health Research Institute La Fe (IIS La Fe), Valencia, Spain., Iborra M; Inflammatory Bowel Disease Research Group, Health Research Institute La Fe (IIS La Fe), Valencia, Spain.; Department of Gastroenterology, Hospital La Fe, Valencia, Spain., Sandoval J; Biomarkers and Precision Medicine Unit, Health Research Institute La Fe (IIS La Fe), Valencia, Spain., Busó E; Central Unit for Research in Medicine (UCIM),University of Valencia, Valencia, Spain., Tortosa L; Inflammatory Bowel Disease Research Group, Health Research Institute La Fe (IIS La Fe), Valencia, Spain., Nos P; Inflammatory Bowel Disease Research Group, Health Research Institute La Fe (IIS La Fe), Valencia, Spain.; Department of Gastroenterology, Hospital La Fe, Valencia, Spain., Beltrán B; Inflammatory Bowel Disease Research Group, Health Research Institute La Fe (IIS La Fe), Valencia, Spain.; Department of Gastroenterology, Hospital La Fe, Valencia, Spain.
Jazyk:	angličtina
Zdroj:	Clinical and translational gastroenterology [Clin Transl Gastroenterol] 2019 Oct; Vol. 10 (10), pp. e00083.
DOI:	10.14309/ctg.0000000000000083
Abstrakt:	Introduction: DNA methylation is an epigenetic mechanism that regulates gene expression and represents an important link between genotype, environment, and disease. It is a reversible and inheritable mechanism that could offer treatment targets. We aimed to assess the methylation changes on specific genes previously associated with Crohn's disease (CD) and to study their possible associations with the pathology. Methods: We included 103 participants and grouped them into 2 cohorts (a first [n = 31] and a second validation [n = 72] cohort), with active CD (aCD) and inactive CD (iCD) and healthy participants (CTR). DNA was obtained from the peripheral blood and analyzed by the Agena platform. The selected genes were catalase (CAT), α-defensin 5 (DEFA5), FasR, FasL, tumor necrosis factor (TNF), TNFRSF1A, TNFRSF1B, PPA2, ABCB1, NOD2, PPARγ, and PKCζ. We used the elastic net algorithm and R software. Results: We studied 240 CpGs. Sixteen CpGs showed differential methylation profiles among aCD, iCD, and CTR. We selected for validation those with the greatest differences: DEFA5 CpG_11; CpG_13; CAT CpG_31.32; TNF CpG_4, CpG_12; and ABCB1 CpG_21. Our results validated the genes DEFA5 (methylation gain) and TNF (methylation loss) with P values < 0.001. In both cases, the methylation level was maintained and did not change with CD activity (aCD vs iCD). The subanalysis comparison between aCD and iCD showed significant differential methylation profiles in other CpGs: TNF, FAS, ABCB1, CAT, and TNFRS1BF genes. Discussion: The methylation status of DEFA5 and TNF genes provides a signature biomarker that characterizes patients with CD and supports the possible implication of the environment and the immune system in CD pathogenesis.
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu