Journal
INTERNATIONAL JOURNAL OF COLORECTAL DISEASE
Volume 25, Issue 5, Pages 553-556Publisher
SPRINGER
DOI: 10.1007/s00384-010-0874-0
Keywords
IRF5; DNA methylation; Inflammatory bowel diseases; Polymorphism
Categories
Funding
- Broad Medical Research Program
- Broad Foundation [IBD-0252]
- Crohn's and Colitis Foundation of America Children's Digestive Health
- Nutrition Foundation/North American Society of Pediatric Gastroenterology Hepatology and Nutrition [2426]
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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. 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. 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. These results implicate that epigenetic dysregulation of the IRF5 promoter is unlikely to be associated with IBD.
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