Section of Pediatric Gastroenterology, Baylor College of Medicine, Houston, TX 77030-2399, USA.
Int J Colorectal Dis. 2010 May;25(5):553-6. doi: 10.1007/s00384-010-0874-0. Epub 2010 Feb 2.
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.
干扰素调节因子 5（IRF5）启动子中的 5 个碱基对插入-缺失（indel）多态性与炎症性肠病（IBD）有关。该多态性为转录因子 SP1 生成了额外的结合位点，并已被证明可增强 IRF5 的表达。此外，它还影响一个 CpG 二核苷酸密集的基因组区域。该 indel 的这些特征表明，它可能影响 IRF5 的表观遗传调控。本研究旨在探讨 5-bp indel 对多态性上游四个 CpG 位点的甲基化模式的潜在影响。还测试了该区域中健康个体和 IBD 个体之间可能存在的 CpG 位点甲基化差异。
通过 33 个外周血白细胞（PBL）DNA 样本中的 4%聚丙烯酰胺凝胶电泳确定基因型。通过亚硫酸氢盐焦磷酸测序测量基因型的 DNA 甲基化相关性。在 87 个个体的 PBL 样本中评估 IRF5 启动子甲基化与疾病状态的关联，其中 49 个为健康个体，18 个为克罗恩病，20 个为溃疡性结肠炎。
该多态性不影响 IRF5 启动子的甲基化模式，我们也无法检测到健康个体和 IBD 个体之间该基因座低甲基化的平均差异。
这些结果表明，IRF5 启动子的表观遗传失调不太可能与 IBD 相关。
