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Analysis of expression of genes involved in celiac disease

ABSTRACT: Celiac disease (CD) is a chronic immune-mediated disorder with an important genetic component. We analyzed the expression of candidate genes in biopsies from duodenum.

ORGANISM(S): Homo sapiens

PROVIDER: GSE84729 | GEO | 2016/10/31

SECONDARY ACCESSION(S): PRJNA330960

REPOSITORIES: GEO

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Expression of candidate genes in Celiac Disease - Associated genes and regulatory elements (part 1)

Project description:Celiac disease is a chronic immune-mediated disorder with an important genetic component. We analyzed the expression of candidate genes and regulatory elements in biopsies from duodenum.

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Project description:Background and aims: Celiac disease is provoked by gluten exposure, but the resultant pathogenic process in the duodenum is not well understood. We aimed to define the core celiac transcriptomic signature and pathologic pathways in pre-treatment diagnostic duodenum biopsies. Methods: We use mRNAseq to define pre-treatment diagnostic duodenum gene expression in 54 pediatric celiac patients and non-celiac controls, and we validate our key findings in an independent cohort of 40 participants. We further define similar and divergent genes and pathways in 177 Crohn disease patients and controls. Results: We observe a marked suppression of mature epithelial metabolic functions in celiac patients, overlapping substantially with the Crohn signature. A marked adaptive immune response was noted for the up-regulated signature including interferon response, alpha-beta, and gamma-delta T-cells that overlapped to some extant with the Crohn signature. However, we identified a celiac specific signature linked to increased cell proliferation, nuclear division, and cell cycle activity that was localized primarily to the epithelia as noted by CCNB1 and Ki67 staining. Lastly, we demonstrate the utility of the transcriptomic date to correctly classify disease or healthy states in the discovery and validation cohorts. Conclusion: Our data provide insights into celiac pathogenesis and can stimulate new approaches to address this highly prevalent condition.

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