In:
Journal of Crohn's and Colitis, Oxford University Press (OUP), Vol. 17, No. 2 ( 2023-03-18), p. 170-184
Kurzfassung:
Epigenetic alterations may provide valuable insights into gene–environment interactions in the pathogenesis of inflammatory bowel disease [IBD]. Methods Genome-wide methylation was measured from peripheral blood using the Illumina 450k platform in a case-control study in an inception cohort (295 controls, 154 Crohn’s disease [CD], 161 ulcerative colitis [UC] , 28 IBD unclassified [IBD-U)] with covariates of age, sex and cell counts, deconvoluted by the Houseman method. Genotyping was performed using Illumina HumanOmniExpressExome-8 BeadChips and gene expression using the Ion AmpliSeq Human Gene Expression Core Panel. Treatment escalation was characterized by the need for biological agents or surgery after initial disease remission. Results A total of 137 differentially methylated positions [DMPs] were identified in IBD, including VMP1/MIR21 [p = 9.11 × 10−15] and RPS6KA2 [6.43 × 10−13], with consistency seen across Scandinavia and the UK. Dysregulated loci demonstrate strong genetic influence, notably VMP1 [p = 1.53 × 10−15] . Age acceleration is seen in IBD [coefficient 0.94, p & lt; 2.2 × 10−16]. Several immuno-active genes demonstrated highly significant correlations between methylation and gene expression in IBD, in particular OSM: IBD r = −0.32, p = 3.64 × 10−7 vs non-IBD r = −0.14, p = 0.77] . Multi-omic integration of the methylome, genome and transcriptome also implicated specific pathways that associate with immune activation, response and regulation at disease inception. At follow-up, a signature of three DMPs [TAP1, TESPA1, RPTOR] were associated with treatment escalation to biological agents or surgery (hazard ratio of 5.19 [CI: 2.14–12.56] , logrank p = 9.70 × 10−4). Conclusion These data demonstrate consistent epigenetic alterations at diagnosis in European patients with IBD, providing insights into the pathogenetic importance and translational potential of epigenetic mapping in complex disease.
Materialart:
Online-Ressource
ISSN:
1873-9946
,
1876-4479
DOI:
10.1093/ecco-jcc/jjac127
Sprache:
Englisch
Verlag:
Oxford University Press (OUP)
Publikationsdatum:
2023
ZDB Id:
2389631-0
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