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A Differential Host Response to Viral Infection Defines a Subset of Earlier-Onset Diverticulitis Patients

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Kathleen M. Schieffer1, Bryan P. Kline1, Leonard R. Harris1, Sue Deiling1, Walter A. Koltun1, Gregory S. Yochum1,2

1) Department of Surgery, Division of Colon and Rectal Surgery, Pennsylvania State University College of Medicine, Hershey,
2) Department of Biochemistry & Molecular Biology, Pennsylvania State University College of Medicine, Hershey, PA, USA

DOI: http://dx.doi.org/10.15403/jgld.2014.1121.273.sch


Background & Aims: Diverticulitis is the chronic inflammation of diverticula. Whether the pathophysiology of earlier-onset patients differs from later-onset patients is unknown. We profiled the colonic transcriptomes of these two patient populations to gain insight into the molecular underpinnings of diverticulitis.

Methods: We conducted deep RNA sequencing (RNA-seq) on colonic segments surgically resected from earlier-onset (<42 years old, n=13) and later-onset (>65 years old, n=13) diverticulitis patients. We used bioinformatic approaches to cluster the patients based on the relationship of differentially expressed genes and to inform on the molecular pathways that segregated the clusters.

Results: Principal component analysis identified three patient clusters; diverticulitis later-onset (DVT-LO), diverticulitis mixed-onset (DVT-MO), and diverticulitis earlier-onset (DVT-EO). The patients comprising DVT-EO, which was the majority of earlier-onset patients, displayed increased expression of anti-viral response genes. This finding was confirmed using an independent weighted co-expression network analysis (WGCNA) of differentially expressed genes.

Conclusions: We found that the majority of patients with earlier-onset disease contained elevated expression of host genes involved in the anti-viral response. Thus, susceptibility to a viral pathogen may offer one explanation why some individuals develop diverticulitis at an earlier age.

Key words: diverticulitis – earlier-onset – RNA-seq – viral response.

Abbreviations: DVT-EO: diverticulitis earlier-onset; DVT-MO: diverticulitis mixed-onset; DVT-LO: diverticulitis later-onset; GO: gene ontology; GTEx: Genotype-Tissue Expression; IBD: inflammatory bowel disease; IFIT: interferon-induced protein with tetratricopeptide; ISG15: interferon-stimulated gene fifteen; ME: module eigengene; OASL: 2’-5’ oligoadenylate synthetase-like; PCA: principal component analysis; RNA-seq: RNA deep sequencing; WGCNA: weighted gene co-expression network analysis.