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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 
Citation
 DIGESTIVE DISEASES AND SCIENCES, Vol.57(10) : 2600-2607, 2012 
Journal Title
 DIGESTIVE DISEASES AND SCIENCES 
ISSN
 0163-2116 
Issue Date
2012
MeSH
Asian Continental Ancestry Group ; Case-Control Studies ; Colon ; DNA/genetics ; DNA Methylation ; Gene Expression Regulation/physiology ; Genetic Predisposition to Disease* ; Genotype ; Humans ; Inflammatory Bowel Diseases/genetics* ; Intestinal Mucosa ; Polymorphism, Genetic ; Promoter Regions, Genetic ; Real-Time Polymerase Chain Reaction ; Reverse Transcriptase Polymerase Chain Reaction ; STAT4 Transcription Factor/genetics ; STAT4 Transcription Factor/metabolism*
Keywords
STAT4 ; Inflammatory bowel disease ; Ulcerative colitis ; Crohn’s disease ; Intestinal Bechet’s disease ; DNA methylation ; Genetic polymorphism
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.
Full Text
http://link.springer.com/article/10.1007%2Fs10620-012-2199-z
DOI
22569826
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Yonsei Biomedical Research Center (연세의생명연구원) > 1. Journal Papers
Yonsei Authors
Kim, Seung Won(김승원) ORCID logo https://orcid.org/0000-0002-1692-1192
Kim, Won Ho(김원호) ORCID logo https://orcid.org/0000-0002-5682-9972
Kim, Eun Soo(김은수)
Kim, Tae Il(김태일) ORCID logo https://orcid.org/0000-0003-4807-890X
Moon, Chang Mo(문창모)
Cheon, Jae Hee(천재희) ORCID logo https://orcid.org/0000-0002-2282-8904
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/90146
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