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Abnormal genetic and epigenetic changes in signal transducer and activator of transcription 4 in the pathogenesis of inflammatory bowel diseases

Title
Abnormal genetic and epigenetic changes in signal transducer and activator of transcription 4 in the pathogenesis of inflammatory bowel diseases
Authors
Kim S.W.Kim E.S.Moon C.M.Kim T.I.Kim W.H.Cheon J.-H.
Ewha Authors
김승원
Issue Date
2012
Journal Title
Digestive Diseases and Sciences
ISSN
0163-2116JCR Link
Citation
vol. 57, no. 10, pp. 2600 - 2607
Indexed
SCI; SCIE; SCOPUS scopus
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. © 2012 Springer Science+Business Media, LLC.
DOI
10.1007/s10620-012-2199-z
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약학대학 > 약학과 > Journal papers
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