Cookies on this website

We use cookies to ensure that we give you the best experience on our website. If you click 'Accept all cookies' we'll assume that you are happy to receive all cookies and you won't see this message again. If you click 'Reject all non-essential cookies' only necessary cookies providing core functionality such as security, network management, and accessibility will be enabled. Click 'Find out more' for information on how to change your cookie settings.

Background & aimsThere is great current interest in the potential application of DNA methylation alterations in peripheral blood leukocytes (PBLs) as biomarkers of susceptibility, progression, and treatment response in inflammatory bowel disease (IBD). However, the intra-individual stability of PBL methylation in IBD has not been characterized. Here, we studied the long-term stability of all probes located on the Illumina HumanMethylation EPIC BeadChip array.MethodsWe followed a cohort of 46 adult patients with IBD (36 Crohn's disease [CD], 10 ulcerative colitis [UC]; median age, 44 years; interquartile range [IQR] 27-56 years; 50% female) that received standard care follow-up at the Amsterdam University Medical Centers. Paired PBL samples were collected at 2 time points with a median of 7 years (range, 2-9 years) in between. Differential methylation and intra-class correlation (ICC) analyses were used to identify time-associated differences and temporally stable CpGs, respectively.ResultsAround 60% of all EPIC array loci presented poor intra-individual stability (ICC <0.50); 78.114 (≈9%) showed good (ICC, 0.75-0.89), and 41.274 (≈5%) showed excellent (ICC ≥0.90) stability, between both measured time points. Focusing on previously identified consistently differentially methylated positions indicated that 22 CD-, 11 UC-, and 24 IBD-associated loci demonstrated high stability (ICC ≥0.75) over time; of these, we observed a marked stability of CpG loci associated to the HLA genes.ConclusionsOur data provide insight into the long-term stability of the PBL DNA methylome within an IBD context, facilitating the selection of biologically relevant and robust IBD-associated epigenetic biomarkers with increased potential for independent validation. These data also have potential implications in understanding disease pathogenesis.

Original publication

DOI

10.1016/j.jcmgh.2022.12.011

Type

Journal article

Journal

Cellular and molecular gastroenterology and hepatology

Publication Date

01/2023

Volume

15

Pages

869 - 885

Addresses

Department of Gastroenterology and Hepatology, Amsterdam Gastroenterology Endocrinology Metabolism, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands.

Keywords

Humans, Colitis, Ulcerative, Inflammatory Bowel Diseases, Crohn Disease, DNA Methylation, Adult, Female, Male