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Digestive Diseases and Sciences

Published in:

01-10-2012 | Original Article

Abnormal Genetic and Epigenetic Changes in Signal Transducer and Activator of Transcription 4 in the Pathogenesis of Inflammatory Bowel Diseases

Authors: Seung Won Kim, Eun Soo Kim, Chang Mo Moon, Tae Il Kim, Won Ho Kim, Jae Hee Cheon

Published in: Digestive Diseases and Sciences | Issue 10/2012

Abstract

Background and Aims

Changes in the expression of signal transducer and activator of transcription 4 (STAT4) contribute to the development of a variety of autoimmune diseases including inflammatory bowel diseases (IBDs). Moreover, epigenetic modifications, including DNA methylation, are considered a basis for differentiation of T helper cells and regulation of cytokines. In this study, we investigated the methylation status of STAT4 gene in IBD patients and the associations between its genetic and epigenetic alterations in IBD patients.

Methods

Blood and colonic mucosa samples were obtained from Korean patients with IBD and healthy controls. Peripheral blood mononuclear cells (PBMCs) were isolated, and total RNA and genomic DNA were isolated from the PBMCs and colon mucosa tissues. The mRNA level and DNA methylation status of the promoter were determined by real-time RT-PCR and pyrosequencing, respectively. The chosen SNPs (rs11889341, rs7574865, rs8179673, rs6752770, rs925847, rs10168266, rs10181656, and rs11685878) were genotyped using the TaqMan nuclease assay.

Results

Elevated expression of STAT4 was observed in the colonic mucosa and PBMCs of IBD patients. IBD patients showed a lower degree of methylation of the STAT4 promoter than did the healthy controls. Moreover, a significant correlation between risk alleles and methylation status at −172 of the STAT4 promoter was observed, and mRNA levels of STAT4 in IBD patients were correlated inversely with the T-risk allele (rs7574865).

Conclusions

Our data demonstrated that the DNA methylation status of STAT4 is associated with genetic polymorphisms, providing insights into the interactions between genetic and epigenetic aberrances in STAT4 that contribute to the development of IBD.

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Title: Abnormal Genetic and Epigenetic Changes in Signal Transducer and Activator of Transcription 4 in the Pathogenesis of Inflammatory Bowel Diseases
Authors: Seung Won Kim
Eun Soo Kim
Chang Mo Moon
Tae Il Kim
Won Ho Kim
Jae Hee Cheon
Publication date: 01-10-2012
Publisher: Springer US
Published in: Digestive Diseases and Sciences / Issue 10/2012
Print ISSN: 0163-2116
Electronic ISSN: 1573-2568
DOI: https://doi.org/10.1007/s10620-012-2199-z

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