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* = Presenting author

P704 RNA sequencing shows transcriptomic changes in affected and unaffected mucosa of Crohn's disease patients compared to normal colonic mucosa of healthy controls.

S.N. Hong*1, J.S. Koo2, S.J. Park3, J.P. Im4, Y.S. Kim5, J.W. Kim4, Y.-H. Kim1

1Samsung Medical Center, Sungkyunkwan University School of Medicine, Medicine, Seoul, South Korea, 2Korea University College of Medicine, Internal Medicine, Ansan, Korea, Republic of, 3Yonsei University, Yonsei university school of medicine, Seoul, Korea, Republic of, 4Seoul National University College of Medicine, Internal Medicine, Seoul, Korea, Republic of, 5Inje University College of Medicine, Internal Medicine, Seoul, Korea, Republic of

Background

Background: Crohn's disease is chronic inflammatory bowel diseases caused by dysregulated mucosal immune responses to the gut microbiota in genetically susceptible individuals. So far, over 140 susceptibility loci to CD have been identified through genome-wide association studies and meta-analyses, however it has not fully explained the heritability of CD. Because a phenotypic character of CD is an abrupt transition between unaffected normal-looking mucosa and affected ulcerative mucosa, so-called skip lesions, the evaluation of transcriptome in affected and unaffected mucosa of CD patients may give a direct evidence for pathogenesis of CD. The aim was to investigate the transcriptomic changes in affected and unaffected mucosa of Crohn's disease patients compared to normal colonic mucosa of healthy controls by using RNA sequencing.

Methods

We conducted a pilot case-control study of RNA expression profile using RNA sequencing of affected ulcerative and unaffected normal-looking intestinal mucosa of 13 CD patients compared to normal colonic mucosa of age/sex matched 13 healthy controls. Mucosal total RNA was isolated and purified, and next-generation pair-end sequencing was performed. After normalization between samples, differentially expressed genes were selected using DESeq R package.

Results

Forty four genes were differentially expressed in affected vs. unaffected CD mucosa (p<0.01), 1,158 genes in affected CD mucosa vs. normal control mucosa (p<0.01), and 182 genes in unaffected CD mucosa vs. normal control mucosa (p<0.01). Nineteen genes were overlapped on Venn Diagram. Fifteen genes were up-regulated sequentially in affected, unaffected CD mucosa, and normal control mucosa (ANGPT2, CHN1, CPXM1, CPZ, CXCL1, FCN3, GJC1, HSD11B1, LZTS1, MEOX1, MMP12, PLA1A, SERPINE1, SGIP1, and TRPC4). Four genes were down-regulated sequentially in normal control mucosa, affected, and unaffected CD mucosa (FAM189A1, PDE6A, SLC38A4, and HMGCS2). Pathway analysis revealed that identified genes were associated with collagen degradation, collagen biosynthesis and modifying enzymes, integrin cell surface interactions, extracellular matrix organization, degradation of the extracellular matrix, validated targets of C-MYC transcriptional activation, collagen formation, and leukocyte transendothelial migration.

Conclusion

RNA-Seq analysis of affected, unaffected CD mucosa, and normal colonic mucosa show transcriptome changes that provide the rationale for validation studies to explore the role of mucosal factors in the pathogenesis of CD.

This study was supported by a grant of the Korean Health Technology R&D Project, Ministry of Health and Welfare, Republic of Korea (A120176).