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Assessment of DNA methylation at the interferon regulatory factor 5 (IRF5) promoter region in inflammatory bowel diseases

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International Journal of Colorectal Disease Aims and scope Submit manuscript

Abstract

Background and aims

A 5-bp insertion–deletion (indel) polymorphism in the promoter of interferon regulatory factor 5 (IRF5) has been associated with inflammatory bowel diseases (IBD). This polymorphism generates an additional binding site for the transcription factor SP1 and has been shown to augment the expression of IRF5. Additionally, it affects a CpG dinucleotide-dense genomic region. These features of the indel suggested that it may influence the epigenetic regulation of IRF5. The aim of this study was to investigate the potential effect of the 5-bp indel on the methylation pattern of four CpG sites upstream of the polymorphism. Possible CpG site methylation differences in this region between healthy persons and individuals suffering from IBD were also tested.

Methods

Genotype was determined by 4% polyacrylamide gel electrophoresis in 33 peripheral blood leukocyte (PBL) DNA samples. DNA methylation correlates of the genotypes were measured by bisulfite pyrosequencing. IRF5 promoter methylation in association to disease state was assessed in 87 proband (49 healthy, 18 Crohn’s disease, 20 ulcerative colitis) PBL samples.

Results

The polymorphism did not affect the methylation pattern of the IRF5 promoter nor could we detect significant differences in the average, low methylation of the locus between healthy persons and individuals with IBD.

Conclusions

These results implicate that epigenetic dysregulation of the IRF5 promoter is unlikely to be associated with IBD.

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Acknowledgments

R.K. was supported by funding from the Broad Medical Research Program, the Broad Foundation (IBD-0252), and a young investigator joint award from the Crohn’s and Colitis Foundation of America—Children’s Digestive Health and Nutrition Foundation/North American Society of Pediatric Gastroenterology Hepatology and Nutrition (CCFA Ref #2426).

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Authors and Affiliations

  1. Section of Pediatric Gastroenterology, Baylor College of Medicine, Houston, TX, USA

    Alfred Balasa & Richard Kellermayer

  2. Section of Digestive Disease, Department of Internal Medicine, Yale University, New Haven, CT, USA

    Grace Gathungu & Judy H. Cho

  3. Department of Medical Genetics, University of Pecs, Pecs, Hungary

    Peter Kisfali & Bela Melegh

  4. USDA Children’s Nutrition Research Center, Houston, TX, USA

    E O’Brian Smith

  5. Section of Pediatric Gastroenterology, Hepatology & Nutrition, Baylor College of Medicine, 6621 Fannin St., CC1010.00, Houston, TX, 77030-2399, USA

    Richard Kellermayer

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  1. Alfred Balasa
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  2. Grace Gathungu
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  3. Peter Kisfali
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  4. E O’Brian Smith
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  5. Judy H. Cho
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  6. Bela Melegh
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  7. Richard Kellermayer
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Correspondence to Richard Kellermayer.

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Balasa, A., Gathungu, G., Kisfali, P. et al. Assessment of DNA methylation at the interferon regulatory factor 5 (IRF5) promoter region in inflammatory bowel diseases. Int J Colorectal Dis 25, 553–556 (2010). https://doi.org/10.1007/s00384-010-0874-0

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  • DOI: https://doi.org/10.1007/s00384-010-0874-0

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